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COVID-19BRAINSTEM-COVNCT04527198

Brainstem Dysfunction in COVID-19 Critically Ill Patients: a Prospective Observational Study

A study testing Brainstem Responses Assessment Sedation Score (BRASS) and Electroencephalogram with EKG lead in people with COVID-19, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine the prevalence of brainstem dysfunction in critically ill ventilated and deeply sedated patients hospitalized in the Intensive Care Unit (ICU) for a SARS-CoV-s2 infection. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19
What is being tested?
Brainstem Responses Assessment Sedation Score (BRASS) and Electroencephalogram with EKG lead
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
2 sitesFrance
Study dates
14 Sep 2020to 31 Dec 2020
Phase
Interventional
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

Who may be able to join

  • ICU hospitalization
  • Invasive mechanical ventilation
  • Deep sedation (RASS<-3) >12 hours
  • Positive SARS-COV-2 PCR

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

France2 sites

  • Hôpital Cochin

    Paris, 75014

  • HEGP

    Paris, 75015

Other trials in France

About this study

Official title: Brainstem Dysfunction in Ventilated and Deeply Sedated COVID-19 Critically Ill Patients: a Prospective Observational Study

The purpose of this study is to determine the prevalence of brainstem dysfunction in critically ill ventilated and deeply sedated patients hospitalized in the Intensive Care Unit (ICU) for a SARS-CoV-s2 infection.

Read the 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.

Conditions
COVID-19
Being tested
Brainstem Responses Assessment Sedation Score (BRASS), Electroencephalogram with EKG lead
Keywords
Brainstem dysfunction, Delirium, Awareness, Arousal, Dysautonomia, Autonomic system, SARS-COV-2, COVID-19, sedation, mechanical ventilation, EEG, EKG
Medical subject headings
COVID-19, Delirium, Autonomic Nervous System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brainstem Responses Assessment Sedation Score (BRASS)Diagnostic test

    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.

  • Electroencephalogram with EKG leadDiagnostic test

    Also called EEG

    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).

Study groups in NCT04527198
Study groupRoleWhat they receive
group 1ExperimentalMajor patients, admitted in intensive care for a SARS-CoV-2 infection and requiring mechanical ventilation and deep sedation (with or without neuromuscular blockade)
Receives: Diagnostic Test: Brainstem Responses Assessment Sedation Score (BRASS); Diagnostic Test: Electroencephalogram with EKG lead

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Brainstem dysfunction prevalence

    Clinical cranial nerves anomalies using validated scale (BRASS score- ranges from 0 to 7 - ) in deeply sedated patient (RASS <-3)

    Measured: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation

Secondary outcomes (17)

  1. Brainstem dysfunction prevalence after sedation weaning

    Clinical cranial nerves anomalies using validated scale (BRASS score)

    Measured: Day 4 to day 7 after sedation weaning

  2. Link between brainstem dysfunction and clinical dysautonomia

    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

    Measured: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessationn

  3. Link between brainstem dysfunction and clinical dysautonomia after sedation weaning

    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

    Measured: 4 to 7 days after sedation weaning

  4. Characterization of brainstem dysfunction in COVID-19 patients: EEG power

    EEG power in delta, theta, alpha, beta and gamma frequency bands according to the presence or absence of brainstem dysfunction and its severity

    Measured: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation

  5. Characterization of brainstem dysfunction in COVID-19 patients: EEG power after sedation weaning

    EEG power in delta, theta, alpha, beta and gamma frequency bands according to the presence or absence of brainstem dysfunction and its severity

    Measured: Day 4 to day 7 after sedation weaning.

  6. Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity

    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

    Measured: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation

  7. Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity, after sedation weaning

    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

    Measured: Day 4 to day 7 after sedation weaning.

  8. Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity

    EEG complexity using Kolmogorov complexity and permutation entropy according to the presence or absence of brainstem dysfunction and its severity

    Measured: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation

  9. Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity after sedation weaning

    EEG complexity using Kolmogorov complexity and permutation entropy according to the presence or absence of brainstem dysfunction and its severity

    Measured: Day 4 to day 7 after sedation weaning.

  10. Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification

    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

    Measured: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation

  11. Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification after sedation weaning

    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

    Measured: Day 4 to day 7 after sedation weaning.

  12. Duration of mechanical ventilation

    Measured: at ICU discharge up to 28 days

  13. Mortality

    Measured: at ICU discharge up to 28 days

  14. Duration of hospitalisation

    Measured: at hospital discharge up to 90 days

  15. Duration of coma, disturbance of consciousness, delirium

    Measured: at ICU discharge up to 28 days

  16. Neurological functional evolution with mRankin

    Using validated functional scale modified Rankin (mRankin) for independence assessment (mRankin ranges from 0 to 6 with higher scores indicating more severe disability)

    Measured: 90 days after inclusion

  17. Neurological functional evolution with GOSE

    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)

    Measured: 90 days after inclusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2020
  2. Study start14 Sep 2020
  3. Primary completion31 Dec 2020
  4. Study completion31 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04527198
Sponsor's protocol ID
APHP200644
Other IDs
2020-A01559-30
Acronym
BRAINSTEM-COV
Status last verified
Mar 2026
First submitted
2 Jun 2020
Last updated
4 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 28441453

  • 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.

    PubMed 35135966

Questions about this trial

What is this clinical trial studying?

A study testing Brainstem Responses Assessment Sedation Score (BRASS) and Electroencephalogram with EKG lead in people with COVID-19, run by Assistance Publique - Hôpitaux de Paris at 2 sites 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 4 inclusion and 8 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 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Brainstem dysfunction prevalence (time frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04527198, which also lists 2 linked publications.

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 4 Mar 2026; AzTrials last refreshed its copy on 28 Oct 2026.

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