Adult Patients With Alteration of ConsciousnessPRORETRONCT02395861
Prognosis of Brain Reflexes
A study testing neuro-electrophysiologic analyses in people with Adult Patients With Alteration of Consciousness and Admitted Into the Intensive Care Unit (ICU), run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Severe diseases in intensive care unit (ICU) patients are associated with a high mortality rate which nevertheless remains difficult to predict. Recently, the abolition of some brainstem reflexes at clinical examination of ICU patients within the first 24 hours after has been shown of prognostic value in ICU patients… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Patients With Alteration of Consciousness, Admitted Into the Intensive Care Unit (ICU)
- What is being tested?
- neuro-electrophysiologic analyses
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteFrance
- Study dates
- Jul 2015to May 2019
- 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
- Adult Medical or surgical, brain-injured or not, patients
- Admitted to the intensive care Unit (ICU)
- Requiring invasive mechanical ventilation for at least 48 hours
- With alteration of consciousness induced by sedatives or not
- Within the 24 hours (± 12) after admission into the ICU
Who cannot join
- Pregnancy
- Post anoxic coma
- Brain death
- Pre-existing neurologic disease disturbing the interpretation of the brainstem reflexes (Guillain-Barre, myasthenia, gravis, brain tumor, inflammatory or degenerating disease of the posterior fossa, acute peripheral neurologic disease)
- Declined participation
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Beaujon Hospital
Clichy, 92
Jean Mantz, MD PhD
About this study
Official title: Evaluation of the Clinical and Electrophysiological Responses of the Brainstem in Patients With Alteration of Consciousness in Relation or Not With Sedation: Prognostic Study of Brain Reflexes
Severe diseases in intensive care unit (ICU) patients are associated with a high mortality rate which nevertheless remains difficult to predict. Recently, the abolition of some brainstem reflexes at clinical examination of ICU patients within the first 24 hours after has been shown of prognostic value in ICU patients requiring sedation. Early abolition of the cough reflex was associated with an increase in mortality and that of the oculocephalic reflex was predictive of coma or delirium after sedation has been stopped. A dysfunction of the brainstem may account for these results and be present in other patient subpopulations, particularly those who do not receive iv sedation or the brain injured patients, who were eluded from the previous study. This dysfunction could take place in the muti-organ failure characteristic of the severe ICU patient. On the other hand, a preliminary study performed on somatosensory evoked potentials has shown that a latency of the P14 wave greater than 16 ms between day 1 and day 3 after admission was associated with death at 28 days. The primary goal of this project is to confirm this hypothesis. By studying the clinical and electrophysiological responses of the brainstem in ICU patients, with or without brain injury, with alteration of consciousness in relation or not with sedation. The other objectives are to determine the correlations between neurophysiological clinical neurological, or neuroradiological data with delirium occurrence.
The main objective of this study is to determine, in ICU patients with or without brain injury and with alteration of consciousness in relation or not with sedation, if abolition of the cough reflex at Day 1 after admission is predictive of mortality at 28 days, independent from cause for admission and severity.
Read the detailed description
Adult Medical or surgical, brain-injured or not, ICU patients requiring invasive mechanical ventilation for at least 48 hours and with alteration of consciousness induced or not by sedatives. Inclusion will take place at the 24th hour (± 12) after admission into the ICU will be enrolled. Those patients with either pregnancy, post anoxic coma, brain death, pre-existing neurologic disease disturbing the interpretation of the brainstem reflexes (Guillain-Barre, myasthenia, gravis, brain tumor, inflammatory or degenerating disease of the posterior fossa, acute peripheral neurologic disease), or declined participation will be excluded.
The measurements will be based on:
D1 : Demographic data, cause for admission, brainstem reflexes, Glasgow Coma Scale score, Confusion Assessment Method for the ICU (CAM-ICU) , Richmond Agitation Sedation Scale (RASS), Behavioral Pain Scale (BPS), simplified index of gravity (IGS 2) score, Sequential Organ Failure Assessment (SOFA) scores, cumulated sedative doses and Secondary Systemic Cerebral Aggressions (ACSOS) parameters D3 : parameters of D1, electrophysiologic analyses: Electroencephalogram (EEG), auditory evoked potentials (EAEP), Somatosensory Evoked Potential (SEP), recording of clinico-biological data, Cognitive evoked potentials (CEP) in patients with consciousness alteration still on mechanical ventilation at day 3.
D1-D28 : date of death, date of extubation, SOFA, CAM-ICU, cumulated doses of sedatives and analgesics, duration of sedation, occurrence of nosocomial pneumonia after Day 2, brain imaging data if available.
D28 : Glasgow Outcome Coma Scale and mini mental state
- Conditions
- Adult Patients With Alteration of Consciousness, Admitted Into the Intensive Care Unit (ICU)
- Being tested
- neuro-electrophysiologic analyses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
neuro-electrophysiologic analysesOther
mismatch negativity (MMN) cognitive evoked potentials (CEP) auditory evoked potentials (AEP)
| Study group | Role | What they receive |
|---|---|---|
| Electrophysiologic analyses | Experimental | Not described Receives: Other: neuro-electrophysiologic analyses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality at Day 28
Measured: day 28
Secondary outcomes (1)
Neurophysiologic response (P14 latency value greater than 16 ms of the SEP of the median nerve)
P14 latency value greater than 16 ms of the SEP of the median nerve
Measured: day 1 and day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2015 (estimated)
- Study startJul 2015
- Primary completionMay 2019 (estimated)
- Study completionMay 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult Patients With Alteration of ConsciousnessStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02395861
- Sponsor's protocol ID
- P120915
- Other IDs
- 2014-A01102-45
- Acronym
- PRORETRO
- Status last verified
- Feb 2019
- First submitted
- 6 Mar 2015
- Last updated
- 19 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Bouchereau E, Pruvost-Robieux E, Siami S, Chaffaut C, Bougle A, Gavaret M, Heming N, Sivanandamoorthy S, Zyss J, Degos V, Kandelman S, Righy Shinotsuka C, Benghanem S, Naccache L, Rohaut B, Hermann B, Azabou E, Chevret S, Sharshar T. Altered lower brainstem neurophysiological response is associated with mortality in deeply sedated critically ill patients. Intensive Care Med. 2025 Jun;51(6):1050-1061. doi: 10.1007/s00134-025-07945-7. Epub 2025 Jun 13.
PubMed 40512201
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Clinical and Electrophysiological Responses of the Brainstem in Patients With Alteration of Consciousness in Relation or Not With Sedation: Prognostic Study of Brain Reflexes
- ClinicalTrials.gov ID
- NCT02395861
- Acronym / sponsor ID
- PRORETRO / P120915
- Conditions
- Adult Patients With Alteration of Consciousness, Admitted Into the Intensive Care Unit (ICU)
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- May 2019 (estimated)
- Study completion
- May 2019 (estimated)
- First posted
- 24 Mar 2015 (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.
Severe diseases in intensive care unit (ICU) patients are associated with a high mortality rate which nevertheless remains difficult to predict. Recently, the abolition of some brainstem reflexes at clinical examination of ICU patients within the first 24 hours after has been shown of prognostic value in ICU patients requiring sedation. Early abolition of the cough reflex was associated with an increase in mortality and that of the oculocephalic reflex was predictive of coma or delirium after sedation has been stopped. A dysfunction of the brainstem may account for these results and be present in other patient subpopulations, particularly those who do not receive iv sedation or the brain injured patients, who were eluded from the previous study. This dysfunction could take place in the muti-organ failure characteristic of the severe ICU patient. On the other hand, a preliminary study performed on somatosensory evoked potentials has shown that a latency of the P14 wave greater than 16 ms between day 1 and day 3 after admission was associated with death at 28 days. The primary goal of this project is to confirm this hypothesis. By studying the clinical and electrophysiological responses of the brainstem in ICU patients, with or without brain injury, with alteration of consciousness in relation or not with sedation. The other objectives are to determine the correlations between neurophysiological clinical neurological, or neuroradiological data with delirium occurrence.
The main objective of this study is to determine, in ICU patients with or without brain injury and with alteration of consciousness in relation or not with sedation, if abolition of the cough reflex at Day 1 after admission is predictive of mortality at 28 days, independent from cause for admission and severity.
Detailed description
Adult Medical or surgical, brain-injured or not, ICU patients requiring invasive mechanical ventilation for at least 48 hours and with alteration of consciousness induced or not by sedatives. Inclusion will take place at the 24th hour (± 12) after admission into the ICU will be enrolled. Those patients with either pregnancy, post anoxic coma, brain death, pre-existing neurologic disease disturbing the interpretation of the brainstem reflexes (Guillain-Barre, myasthenia, gravis, brain tumor, inflammatory or degenerating disease of the posterior fossa, acute peripheral neurologic disease), or declined participation will be excluded.
The measurements will be based on:
D1 : Demographic data, cause for admission, brainstem reflexes, Glasgow Coma Scale score, Confusion Assessment Method for the ICU (CAM-ICU) , Richmond Agitation Sedation Scale (RASS), Behavioral Pain Scale (BPS), simplified index of gravity (IGS 2) score, Sequential Organ Failure Assessment (SOFA) scores, cumulated sedative doses and Secondary Systemic Cerebral Aggressions (ACSOS) parameters D3 : parameters of D1, electrophysiologic analyses: Electroencephalogram (EEG), auditory evoked potentials (EAEP), Somatosensory Evoked Potential (SEP), recording of clinico-biological data, Cognitive evoked potentials (CEP) in patients with consciousness alteration still on mechanical ventilation at day 3.
D1-D28 : date of death, date of extubation, SOFA, CAM-ICU, cumulated doses of sedatives and analgesics, duration of sedation, occurrence of nosocomial pneumonia after Day 2, brain imaging data if available.
D28 : Glasgow Outcome Coma Scale and mini mental state
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Electrophysiologic analyses | Experimental | Other: neuro-electrophysiologic analyses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult Medical or surgical, brain-injured or not, patients
- Admitted to the intensive care Unit (ICU)
- Requiring invasive mechanical ventilation for at least 48 hours
- With alteration of consciousness induced by sedatives or not
- Within the 24 hours (± 12) after admission into the ICU
Key exclusion criteria (5 listed)
- Pregnancy
- Post anoxic coma
- Brain death
- Pre-existing neurologic disease disturbing the interpretation of the brainstem reflexes (Guillain-Barre, myasthenia, gravis, brain tumor, inflammatory or degenerating disease of the posterior fossa, acute peripheral neurologic disease)
- Declined participation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| neuro-electrophysiologic analysesmismatch negativity (MMN) cognitive evoked potentials (CEP) auditory evoked potentials (AEP) | Other | Electrophysiologic analyses |
Primary outcome
Mortality at Day 28
Time frame: day 28
1 secondary outcome
Neurophysiologic response (P14 latency value greater than 16 ms of the SEP of the median nerve)
Time frame: day 1 and day 3
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
- Derived from this study: PubMed 40512201Bouchereau E, Pruvost-Robieux E, Siami S, Chaffaut C, Bougle A, Gavaret M, Heming N, Sivanandamoorthy S, Zyss J, Degos V, Kandelman S, Righy Shinotsuka C, Benghanem S, Naccache L, Rohaut B, Hermann B, Azabou E, Chevret S, Sharshar T. Altered lower brainstem neurophysiological response is associated with mortality in deeply sedated critically ill patients. Intensive Care Med. 2025 Jun;51(6):1050-1061. doi: 10.1007/s00134-025-07945-7. Epub 2025 Jun 13.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing neuro-electrophysiologic analyses in people with Adult Patients With Alteration of Consciousness and Admitted Into the Intensive Care Unit (ICU), 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 5 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 19 Feb 2019. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean MANTZ, MD PhD (33+1 40875911, jean.mantz@bjn.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality at Day 28 (time frame: day 28). 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 NCT02395861, which also lists 1 linked publication.
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 19 Feb 2019.