Clinical trial NCT04320472: Acute Encephalopathy in Critically Ill Patients With COVID-19
Official title: Outcomes in Patients With Acute Encephalopathy and SARS-Cov-2 Infection
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Encephalopathy
Critically Ill
Lead sponsor: Ictal Group
Sponsor class: OTHER
First posted: 2020-03-25
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Acute encephalopathy and ICU admission

Brief summary: Infection with SARS-CoV-2 or severe acute respiratory syndrome coronarvirus type 2 was highlighted in December 2019 in the city of Wuhan in China, responsible for an pandemic evolution since March 11, 2020. The infection affects all ages of life, although affecting children in a very small proportion of cases. The typical presentation of the disease combines fever (98%), cough (76%), myalgia and asthenia (18%) as well as leukopenia (25%) and lymphopenia (63%). Upper airway involvement rare.

The main clinical presentation requiring hospitalization of infected patients is that of atypical pneumonia which may require critical care management (27%), and progress to an acute respiratory distress syndrome (67%) involving life-threatening conditions in almost 25% of patients diagnosed with SARS-CoV-2 infection. Other organ damage have been reported, mainly concerning kidney damage (29%) which may require renal replacement therapy in approximately 17% of patients.

Neurological damage has been very rarely studied, yet reported in 36% of cases in a study including patients of varying severity.

Finally, the mortality associated with this emerging virus is high in patients for whom critical care management is necessary, reported in 62% of patients.

We therefore propose a prospective observational study which aim at reporting the prevalence of acute encephalopathy at initial management in Critical/Intensive care or Neurocritical care , to report its morbidity and mortality and to identify prognostic factors.

Detailed description: All patients with SARS-CoV-2 infection and acute encephalopathy at presentation will be prospectively included in the NEURO-COVD-19 study. This study will collect demographic data, clinical examen at prehospital/emergency room and ICU admission (including neurological signs), and all ancillary exams performed to identify a cause of neurological impairment. Outcome will be evaluated using the Glasgow Outcome Scale score at ICU and hospital discharge, and day-90 after ICU admission.

Acute encephalopathy will be defined as recently stated :

"1. The term acute encephalopathy refers to a rapidly developing (over less than 4 weeks, but usually within hours to a few days) pathobiological process in the brain. This is a preferred term 2. Acute encephalopathy can lead to a clinical presentation of subsyndromal delirium, delirium, or in case of a severely decreased level of consciousness, coma; all representing a change from baseline cognitive status 3. The term delirium refers to a clinical state characterized by a combination of features defined by diagnostic systems such as the DSM-5. Delirium according to the DSM-5 is defined if criterium A-E are fulfilled: A. Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment). B. The disturbance develops over a short period of time (usually hours to a few days) represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of the day. C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception). D. The disturbances in criteria A and C are not explained by another pre-existing, established, or evolving neurocognitive disorder, and do not occur in the context of a severely reduced level of arousal, such as coma. E. There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiologic consequence of another medical condition, substance intoxication or withdrawal (i.e. because of a drug of abuse medication), or exposure to a toxin, or is because of multiple etiologies. " (Slooter, A.J.C., Otte, W.M., Devlin, J.W. et al. Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies. Intensive Care Med (2020). https://doi.org/10.1007/s00134-019-05907-4)

Eligibility criteria: Inclusion Criteria:

* Critical/Intensive care or Neurocritical care admission
* Admission for/with acute encephalopathy defined as a rapidly developing (over less than 4 weeks, but usually within hours to a few days) pathobiological process in the brain; including delirium or subsyndromal (DSM V definition) or coma (Glasgow coma scale score \< 9)
* SARS-COV-2 infection (respiratory or other PCR specimen)
* Age ≥ 18 years

Exclusion Criteria:

- Opposition to study participation from the patient itself or patient surrogate

Primary outcomes:
measure: prevalence
timeFrame: at Critical/Intensive care or Neurocritical care admission
Secondary outcomes:
measure: Favorable outcome
timeFrame: 3 months
measure: Favorable outcome
timeFrame: 3 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: Jackson Memorial Health System; University of Miami, Miller School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Wellstar Atlanta Medical Center
state: Georgia
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo
city: Cali
country: Colombia
facility: Fundación Valle del Lili, University Hospital
city: Cairo
country: Egypt
facility: Cairo University Hospitals
city: Argenteuil
country: France
facility: Centre Hospitalier d'Argenteuil
city: Beauvais
country: France
facility: Centre Hospitalier de Beauvais
city: Boulogne
country: France
facility: Centre Hospitalier Universitaire Ambroise Paré
city: Bourg-en-Bresse
country: France
facility: Centre Hospitalier de Bourg en Bresse
city: Brest
country: France
facility: Centre Hospitalier Régional Universitaire de Brest
city: Brive-la-Gaillarde
country: France
facility: Centre Hospitalier de Brives
city: Clichy
country: France
facility: Centre Hospitalier Universitaire Beaujon
city: Colombes
country: France
facility: Centre Hospitalier Universitaire Louis Mourier
city: Créteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Dieppe
country: France
facility: Centre hospitalier de Dieppe
city: Dijon
country: France
facility: Centre Hospitalier Universitaire de Dijon
city: Etampes
country: France
facility: Centre Hospitalier d'Etampes
city: Jossigny
country: France
facility: Grand Hôpital de l'Est Francilien - Site de Marne-la-Vallée
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier de la Roche-sur-Yon
city: La Rochelle
country: France
facility: Centre Hospitalier de La Rochelle
city: Le Chesnay
country: France
facility: Centre Hospitalier de Versailles
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille
city: Lyon
country: France
facility: Centre Hospitalier Universitaire Hôpital Edouard Herriot
city: Massy
country: France
facility: Hôpital privé Jacques Cartier
city: Melun
country: France
facility: Groupe Hospitalier Sud Ile-de-France
city: Orléans
country: France
facility: Centre Hospitalier Régional d'Orléans
city: Paris
country: France
facility: Centre Hospitalier Universitaire Cochin
city: Paris
country: France
facility: Groupe hospitalier Paris Saint-Joseph
city: Paris
country: France
facility: Hôpital Fondation Adolphe de Rothschild
city: Quincy-sous-Sénart
country: France
facility: Hopital Privé Claude Galien
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes
city: Roanne
country: France
facility: Centre Hospitalier de Roanne
city: Suresnes
country: France
facility: Hopital Foch
city: Toulon
country: France
facility: Centre Hospitalier de Toulon
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse
city: Tours
country: France
facility: Centre Hospitalier Universitaire de Tours
city: Villejuif
country: France
facility: Gustave-Roussy
city: Guanajuato
country: Mexico
facility: Hospital Regional De Alta Especialidad Del Bajío
city: Valencia
country: Spain
facility: Hospital Clinic Universitari
Study officials:
affiliation: Ictal Group
name: Stephane LEGRIEL, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: