Sepsis-Associated EncephalopathyNCT04870983
The Dynamic Change of MMN in Patients With Sepsis Associated Encephalopathy
An observational study of Sepsis-Associated Encephalopathy and Mismatch Negativity, run by Chinese Medical Association at 1 site in China.
Trial summary
Sepsis-associated encephalopathy (SAE), is one of the most common organ dysfunction during the acute phase in sepsis and septic shock. Electroencephalogram (EEG) and auditory evoked potentials (AEPs), which reflect different aspects of brain function, are the most commonly used neurophysiological indices to detect… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Sepsis-Associated Encephalopathy, Mismatch Negativity
- How many people
- 84 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2021to 1 Feb 2022
- How long will I take part?
- 1 Month
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients with confirmed sepsis or septic shock
Who may be able to join
- ages between 18 and 80 years;
- expected stay in the ICU of > 72 h;
- patients diagnosed with sepsis or septic shock;
- informed consent was signed by the patient or relatives;
Who cannot join
- at terminal stage of disease;
- primary brain injury (such as traumatic brain injury, stroke, cardiac arrest, intracranial infection, epilepsy, Alzheimer's disease, Parkinson disease and meningitis etc.);
- acute mental deterioration secondary to non-septic metabolic disorders with organ dysfunction (hepatic encephalopathy, pulmonary encephalopathy, severe electrolyte imbalance, severe blood glucose disorders etc.);
- history of craniocerebral surgery;
- psychiatric illness;
- use of psychiatric medications;
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- impaired hearing; participated in other clinical trial;
- pregnant or lactating women;
- expected death within 72 h after admission.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210008
Beiyuan Zhang, M.S., 15005170137, 1083537599@qq.com
About this study
Official title: The Dynamic Change of Mismatch Negativity is More Associated With Sepsis Associated Encephalopathy and Prognosis at Discharge
Sepsis-associated encephalopathy (SAE), is one of the most common organ dysfunction during the acute phase in sepsis and septic shock. Electroencephalogram (EEG) and auditory evoked potentials (AEPs), which reflect different aspects of brain function, are the most commonly used neurophysiological indices to detect acute brain dysfunction in critically ill patients including sepsis and septic shock. AEPs show the systemic responsiveness of the central nervous to auditory stimuli, so they can be considered a direct measure of brain responsiveness. Mismatch negativity (MMN) is a change-specific component of ERPs, which elicited by a deviant stimulus occurring in a sequence of repetitive stimuli. This component is thought to represent the automatic and unconscious detection of acoustic changes which requires good perceptual discriminative capacity and iconic memory. The peaks of MMN appear at 100 ~ 250 ms from deviant stimulus onset; with increasing magnitude of stimulus change, the peak latency of MMN was shortened and the amplitude increased. Since MMN can be elicited even in the absence of attention, subjects do not need to actively participate. The MMN has been extensively demonstrated to be used in the prediction of awakening in comatose patients for various reasons, and also has been reported to predict awakening in deeply sedated critically ill patients recently. However, it remains unclear whether SAE affects MMN in amplitude and latency that reflects cognitive processing of the auditory information.
Patients with sepsis and septic shock who met the inclusion criteria were screened daily on the CAM-ICU scale, and those with positive CAM-ICU were diagnosed with SAE.All patients were tested for event-evoked potentials on Day 1 and Day 3 after inclusion and were followed up to Day 28 after discharge. The investigators intend to observe the dynamic change of MMN amplitude and latency between SAE and non-SAE groups. Logic regression analysis was used to determine whether the change of MMN was a predictor of SAE.
Read the detailed description
Patient characteristics (including age and sex), date and time of ICU admission, category of admission (medical, surgical or emergency), main reasons for admission, co-morbidities, complications and duration of sepsis before admission were collected. The severity of illness assessed by the acute physiology and chronic health evaluation scoring system (APACHE) II and sequential organ failure assessment (SOFA) score, bladder temperature, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), the level of consciousness assessed by the GCS score, mechanical ventilation (MV) or not, the depth of sedation assessed by RASS, and dose of sedative drugs at 1 and 3 days after admission were also collected.The EEG signal was recorded on the 1st and 3rd day after admission using silver-silver chloride disc electrodes placed on the scalp according to the international 10-20 system. Four electrode locations (left frontal [F3], right frontal [F4], frontal midpoint [Fz] and central [Cz]) were used. All electrodes were referred to the both earlobe and the ground electrode on the forehead. The electrode-skin impedances were kept below 5 kΩ. The EEG signal was amplified and digitized continuously at 279 Hz using EMMA (ERP measuring machine; developed and custom-made in the Department of reinject Medical Equipment Co., Ltd, Guangzhou, China) Background EEG was recorded for 10 min during sleep and/or while the patients lay motionless with their eyes closed in a quiet room. Auditory stimulation was then set to 'on' so that ERPs could be recorded. The stimulation was applied according to an oddball paradigm, which consisted of 85% standard (800 Hz) and 15% deviant (560 Hz) stimuli, with an interstimulus interval of 1 s. The duration of each stimulus was 84 ms, including 7 ms rise and fall times. Altogether 600 stimuli were delivered through earphones to the right ear for each measurement, corresponding to a recording time of about 10 min. The stimulus intensity was set at 75 dB. According to the patient's original EEG, the investigators recorded the main components of the background wave, whether there was periodic discharge and low voltage.The amplitude and latency of MMN components of the event evoked potential.
- Medical subject headings
- Sepsis-Associated Encephalopathy
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 |
|---|---|---|
| SAE group | SAE was defined as cerebral dysfunction in the presence of sepsis or septic shock and the absence of any of the exclusion criteria. For patients undergoing sedation during the ICU stay, the GCS scores were evaluated before sedation; for patients who have been sedated prior to ICU admission, the assumed GCS scores, i.e., the scores measured before any administration of sedative/relaxant drug were used for analysing; for postoperative patients, the GCS scores measured before surgery was used. The CAM-ICU was assessed daily by the nurse or the physician in charge of the patient during the ICU stay. For patients who were sedated, spontaneous awakening trials were performed daily; the longest evaluate time after withdrawal of sedation was 24 h during the trials. In this evaluation period, patients should be awake to evaluate their consciousness, and they were diagnosed of SAE if the patients were not awake. | |
| non-SAE group | The patient was diagnosed with sepsis or septic shock but could not be diagnosed with SAE |
What is being measured
The primary outcome is the main question the study is designed to answer.
the dynamic change of mismatch negativity(MMN) amplitude
μv
Measured: Day 1 and day 3 after admission
the dynamic change of MMN incubation period
ms
Measured: Day 1 and day 3 after admission
Secondary outcomes (3)
Burst suppression
Yes or no
Measured: Day 1 and day 3 after admission
Periodic discharges
Yes or no
Measured: Day 1 and day 3 after admission
Normal background
Yes or no
Measured: Day 1 and day 3 after admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2021
- Study start1 Feb 2021
- Primary completion1 Feb 2022 (estimated)
- Study completion1 Feb 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sepsis-Associated EncephalopathyStudies of the same condition, open and under way.
- 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
- 84 participants (estimated)
- Target duration
- 1 Month
Sponsor and investigators
- Lead sponsor
- Chinese Medical Association
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Wenkui Yu, M.D., Study director, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04870983
- Sponsor's protocol ID
- MMN in SAE
- Status last verified
- Apr 2021
- First submitted
- 19 Apr 2021
- Last updated
- 4 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is not yet known if there will be a plan to make IPD available
Publications
Cotena S, Piazza O. Sepsis-associated encephalopathy. Transl Med UniSa. 2012 Jan 18;2:20-7. Print 2012 Jan.
PubMed 23905041Azabou E, Rohaut B, Porcher R, Heming N, Kandelman S, Allary J, Moneger G, Faugeras F, Sitt JD, Annane D, Lofaso F, Chretien F, Mantz J, Naccache L, Sharshar T; GENeR** (Groupe d'Explorations Neurologiques en Reanimation). Mismatch negativity to predict subsequent awakening in deeply sedated critically ill patients. Br J Anaesth. 2018 Dec;121(6):1290-1297. doi: 10.1016/j.bja.2018.06.029. Epub 2018 Sep 4.
PubMed 30442256Rinaldi S, Consales G, De Gaudio AR. Changes in auditory evoked potentials induced by postsurgical sepsis. Minerva Anestesiol. 2008 Jun;74(6):245-50. Epub 2008 Apr 30.
PubMed 18438333
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Dynamic Change of Mismatch Negativity is More Associated With Sepsis Associated Encephalopathy and Prognosis at Discharge
- ClinicalTrials.gov ID
- NCT04870983
- Acronym / sponsor ID
- MMN in SAE
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Chinese Medical AssociationResearch network
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 1 Feb 2022 (estimated)
- Study completion
- 1 Feb 2022 (estimated)
- First posted
- 4 May 2021 (actual)
- 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.
Sepsis-associated encephalopathy (SAE), is one of the most common organ dysfunction during the acute phase in sepsis and septic shock. Electroencephalogram (EEG) and auditory evoked potentials (AEPs), which reflect different aspects of brain function, are the most commonly used neurophysiological indices to detect acute brain dysfunction in critically ill patients including sepsis and septic shock. AEPs show the systemic responsiveness of the central nervous to auditory stimuli, so they can be considered a direct measure of brain responsiveness. Mismatch negativity (MMN) is a change-specific component of ERPs, which elicited by a deviant stimulus occurring in a sequence of repetitive stimuli. This component is thought to represent the automatic and unconscious detection of acoustic changes which requires good perceptual discriminative capacity and iconic memory. The peaks of MMN appear at 100 ~ 250 ms from deviant stimulus onset; with increasing magnitude of stimulus change, the peak latency of MMN was shortened and the amplitude increased. Since MMN can be elicited even in the absence of attention, subjects do not need to actively participate. The MMN has been extensively demonstrated to be used in the prediction of awakening in comatose patients for various reasons, and also has been reported to predict awakening in deeply sedated critically ill patients recently. However, it remains unclear whether SAE affects MMN in amplitude and latency that reflects cognitive processing of the auditory information.
Patients with sepsis and septic shock who met the inclusion criteria were screened daily on the CAM-ICU scale, and those with positive CAM-ICU were diagnosed with SAE.All patients were tested for event-evoked potentials on Day 1 and Day 3 after inclusion and were followed up to Day 28 after discharge. The investigators intend to observe the dynamic change of MMN amplitude and latency between SAE and non-SAE groups. Logic regression analysis was used to determine whether the change of MMN was a predictor of SAE.
Detailed description
Patient characteristics (including age and sex), date and time of ICU admission, category of admission (medical, surgical or emergency), main reasons for admission, co-morbidities, complications and duration of sepsis before admission were collected. The severity of illness assessed by the acute physiology and chronic health evaluation scoring system (APACHE) II and sequential organ failure assessment (SOFA) score, bladder temperature, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), the level of consciousness assessed by the GCS score, mechanical ventilation (MV) or not, the depth of sedation assessed by RASS, and dose of sedative drugs at 1 and 3 days after admission were also collected.The EEG signal was recorded on the 1st and 3rd day after admission using silver-silver chloride disc electrodes placed on the scalp according to the international 10-20 system. Four electrode locations (left frontal [F3], right frontal [F4], frontal midpoint [Fz] and central [Cz]) were used. All electrodes were referred to the both earlobe and the ground electrode on the forehead. The electrode-skin impedances were kept below 5 kΩ. The EEG signal was amplified and digitized continuously at 279 Hz using EMMA (ERP measuring machine; developed and custom-made in the Department of reinject Medical Equipment Co., Ltd, Guangzhou, China) Background EEG was recorded for 10 min during sleep and/or while the patients lay motionless with their eyes closed in a quiet room. Auditory stimulation was then set to 'on' so that ERPs could be recorded. The stimulation was applied according to an oddball paradigm, which consisted of 85% standard (800 Hz) and 15% deviant (560 Hz) stimuli, with an interstimulus interval of 1 s. The duration of each stimulus was 84 ms, including 7 ms rise and fall times. Altogether 600 stimuli were delivered through earphones to the right ear for each measurement, corresponding to a recording time of about 10 min. The stimulus intensity was set at 75 dB. According to the patient's original EEG, the investigators recorded the main components of the background wave, whether there was periodic discharge and low voltage.The amplitude and latency of MMN components of the event evoked potential.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Month
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SAE group | – | –SAE was defined as cerebral dysfunction in the presence of sepsis or septic shock and the absence of any of the exclusion criteria. For patients undergoing sedation during the ICU stay, the GCS scores were evaluated before sedation; for patients who have been sedated prior to ICU admission, the assumed GCS scores, i.e., the scores measured before any administration of sedative/relaxant drug were used for analysing; for postoperative patients, the GCS scores measured before surgery was used. The CAM-ICU was assessed daily by the nurse or the physician in charge of the patient during the ICU stay. For patients who were sedated, spontaneous awakening trials were performed daily; the longest evaluate time after withdrawal of sedation was 24 h during the trials. In this evaluation period, patients should be awake to evaluate their consciousness, and they were diagnosed of SAE if the patients were not awake. |
| non-SAE group | – | –The patient was diagnosed with sepsis or septic shock but could not be diagnosed with SAE |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with confirmed sepsis or septic shock
Key inclusion criteria (4 listed)
- ages between 18 and 80 years;
- expected stay in the ICU of > 72 h;
- patients diagnosed with sepsis or septic shock;
- informed consent was signed by the patient or relatives;
Key exclusion criteria (9 listed)
- at terminal stage of disease;
- primary brain injury (such as traumatic brain injury, stroke, cardiac arrest, intracranial infection, epilepsy, Alzheimer's disease, Parkinson disease and meningitis etc.);
- acute mental deterioration secondary to non-septic metabolic disorders with organ dysfunction (hepatic encephalopathy, pulmonary encephalopathy, severe electrolyte imbalance, severe blood glucose disorders etc.);
- history of craniocerebral surgery;
- psychiatric illness;
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
the dynamic change of mismatch negativity(MMN) amplitude
Time frame: Day 1 and day 3 after admission
μv
the dynamic change of MMN incubation period
Time frame: Day 1 and day 3 after admission
ms
3 secondary outcomes
Burst suppression
Time frame: Day 1 and day 3 after admission
Periodic discharges
Time frame: Day 1 and day 3 after admission
Normal background
Time frame: Day 1 and day 3 after admission
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2021.
- Results publication: PubMed 23905041Cotena S, Piazza O. Sepsis-associated encephalopathy. Transl Med UniSa. 2012 Jan 18;2:20-7. Print 2012 Jan.
- Results publication: PubMed 30442256Azabou E, Rohaut B, Porcher R, Heming N, Kandelman S, Allary J, Moneger G, Faugeras F, Sitt JD, Annane D, Lofaso F, Chretien F, Mantz J, Naccache L, Sharshar T; GENeR** (Groupe d'Explorations Neurologiques en Reanimation). Mismatch negativity to predict subsequent awakening in deeply sedated critically ill patients. Br J Anaesth. 2018 Dec;121(6):1290-1297. doi: 10.1016/j.bja.2018.06.029. Epub 2018 Sep 4.
- Results publication: PubMed 18438333Rinaldi S, Consales G, De Gaudio AR. Changes in auditory evoked potentials induced by postsurgical sepsis. Minerva Anestesiol. 2008 Jun;74(6):245-50. Epub 2008 Apr 30.
- Individual participant dataSharing planned: Undecided. It is not yet known if there will be a plan to make IPD available
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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.
Wenkui Yu, M.D. study director
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
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 Sepsis-Associated Encephalopathy and Mismatch Negativity, run by Chinese Medical Association at 1 site in China.
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 9 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 4 May 2021. 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 China. 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 Beiyuan Zhang, M.S. (+86-025-83106666-40400, 1083537599@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the dynamic change of mismatch negativity(MMN) amplitude (time frame: Day 1 and day 3 after admission). The study lists 2 primary outcomes in all. 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 NCT04870983, which also lists 3 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 May 2021.