- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04527198
Brainstem Dysfunction in COVID-19 Critically Ill Patients: a Prospective Observational Study (BRAINSTEM-COV)
Brainstem Dysfunction in Ventilated and Deeply Sedated COVID-19 Critically Ill Patients: a Prospective Observational Study
Study Overview
Status
Conditions
Detailed Description
The recent development of the pandemic due to the SARS-CoV-2 virus has showed that a substantial proportion of patients developed a severe condition requiring critical care, notably because of acute respiratory distress syndrome requiring mechanical ventilation and deep sedation. Outside of this coronavirus infection, this situation is classically associated with a high prevalence of brainstem dysfunction, even in the absence of brain injury. This dysfunction, either structural or functional, can be detected using appropriate clinical tools such as the BRASS score and/or using the quantitative analysis of EKG and EEG. Crucially, brainstem dysfunction is associated not only with ICU complications such as delirium, but also with a poorer survival.
Moreover, some reports of encephalitis cases and the presence of anosmia/agueusia raised the question of whether the virus could directly invade the central nervous system.
For these two reasons, it is reasonable to assume that brainstem dysfunction is particularly prevalent in critically ill patients infected with SARS-CoV-2 and that this dysfunction could be one of the major determinant of patients outcome.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Paris, France, 75014
- Hopital Cochin
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Paris, France, 75015
- HEGP
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- ICU hospitalization
- Invasive mechanical ventilation
- Deep sedation (RASS<-3) >12 hours
- Positive SARS-COV-2 PCR
Exclusion Criteria:
- History of neurologic disease (stroke, degenerative disease)
- Pregnant women
- Moribund patients
- Minor patient
- Major patient under guardianship or curatorship
- Prior inclusion in the study
- Patient not affiliated to a social security scheme
- Limitations and cessation of active therapies
Study Plan
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: group 1
Major patients, admitted in intensive care for a SARS-CoV-2 infection and requiring mechanical ventilation and deep sedation (with or without neuromuscular blockade)
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It consists of a standardized evaluation of brainstem reflexes with a score of 1 attributed for absence of pupillary light reflex, cough reflex and the combined absence of grimace and oculocephalic reflex, a score of 2 for absent corneal reflex and a score of 3 for absent grimace in the presence of oculocephalic The resulting sum ranges from 0 to 7. It will be performed at two times points: a first time under sedation and a second time 3 to 5 days after sedation weaning. A 20 minutes clinical (12 electrodes) EEG with an EKG lead will be performed a first time under sedation and a second time 3 to 5 days after sedation weaning. These EEG recordings will allow to measure the sympathic-parasympathetic ratio using spectral analysis of the EKG and also to measure quantitative markers of brain EEG activity (spectral power and connectivity in delta, theta, alpha, beta and gamma band; complexity).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brainstem dysfunction prevalence
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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Clinical cranial nerves anomalies using validated scale (BRASS score- ranges from 0 to 7 - ) in deeply sedated patient (RASS <-3)
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At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brainstem dysfunction prevalence after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning
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Clinical cranial nerves anomalies using validated scale (BRASS score)
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Day 4 to day 7 after sedation weaning
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Link between brainstem dysfunction and clinical dysautonomia
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessationn
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Analysis of the sympathico-parasympathetic ratio (using spectral analysis of the EKG signal) according to the presence or absence of brainstem dysfunction and its severity
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At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessationn
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Link between brainstem dysfunction and clinical dysautonomia after sedation weaning
Time Frame: 4 to 7 days after sedation weaning
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Analysis of the sympathico-parasympathetic ratio (using spectral analysis of the EKG signal) according to the presence or absence of brainstem dysfunction and its severity
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4 to 7 days after sedation weaning
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Characterization of brainstem dysfunction in COVID-19 patients: EEG power
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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EEG power in delta, theta, alpha, beta and gamma frequency bands according to the presence or absence of brainstem dysfunction and its severity
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At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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Characterization of brainstem dysfunction in COVID-19 patients: EEG power after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning.
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EEG power in delta, theta, alpha, beta and gamma frequency bands according to the presence or absence of brainstem dysfunction and its severity
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Day 4 to day 7 after sedation weaning.
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Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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EEG functional connectivity using weighted Symbolic Mutual Information and weighted Phase Lag Index according to the presence or absence of brainstem dysfunction and its severity
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At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity, after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning.
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EEG functional connectivity using weighted Symbolic Mutual Information and weighted Phase Lag Index according to the presence or absence of brainstem dysfunction and its severity
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Day 4 to day 7 after sedation weaning.
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Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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EEG complexity using Kolmogorov complexity and permutation entropy according to the presence or absence of brainstem dysfunction and its severity
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At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning.
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EEG complexity using Kolmogorov complexity and permutation entropy according to the presence or absence of brainstem dysfunction and its severity
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Day 4 to day 7 after sedation weaning.
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Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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Multivariate classification of the presence or absence of brainstem dysfunction using support vector machine and extra-trees algorithm based on the EEG derived quantitative features presented above
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At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
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Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning.
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Multivariate classification of the presence or absence of brainstem dysfunction using support vector machine and extra-trees algorithm based on the EEG derived quantitative features presented above
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Day 4 to day 7 after sedation weaning.
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Duration of mechanical ventilation
Time Frame: at ICU discharge up to 28 days
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at ICU discharge up to 28 days
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Mortality
Time Frame: at ICU discharge up to 28 days
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at ICU discharge up to 28 days
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Duration of hospitalisation
Time Frame: at hospital discharge up to 90 days
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at hospital discharge up to 90 days
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Duration of coma, disturbance of consciousness, delirium
Time Frame: at ICU discharge up to 28 days
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at ICU discharge up to 28 days
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Neurological functional evolution with mRankin
Time Frame: 90 days after inclusion
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Using validated functional scale modified Rankin (mRankin) for independence assessment (mRankin ranges from 0 to 6 with higher scores indicating more severe disability)
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90 days after inclusion
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Neurological functional evolution with GOSE
Time Frame: 90 days after inclusion
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Using validated functional scale Glasgow Outcome Scale Extended (GOSE) for independence assessment (GOSE ranges from 1 to 8 with higher scores indicating less severe disability outcome)
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90 days after inclusion
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Collaborators and Investigators
Investigators
- Principal Investigator: Bertrand HERMANN, MD, PhD, Assistance Publique - Hôpitaux de Paris
Publications and helpful links
General Publications
- Rohaut B, Porcher R, Hissem T, Heming N, Chillet P, Djedaini K, Moneger G, Kandelman S, Allary J, Cariou A, Sonneville R, Polito A, Antona M, Azabou E, Annane D, Siami S, Chretien F, Mantz J, Sharshar T; Groupe d'Exploration Neurologique en Reanimation (GENER). Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality. PLoS One. 2017 Apr 25;12(4):e0176012. doi: 10.1371/journal.pone.0176012. eCollection 2017.
- Benghanem S, Cariou A, Diehl JL, Marchi A, Charpentier J, Augy JL, Hauw-Berlemont C, Gavaret M, Pene F, Mira JP, Sharshar T, Hermann B. Early Clinical and Electrophysiological Brain Dysfunction Is Associated With ICU Outcomes in COVID-19 Critically Ill Patients With Acute Respiratory Distress Syndrome: A Prospective Bicentric Observational Study. Crit Care Med. 2022 Jul 1;50(7):1103-1115. doi: 10.1097/CCM.0000000000005491. Epub 2022 Feb 9.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- APHP200644
- 2020-A01559-30 (REGISTRY: ID-RCB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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