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Critical IllnessCLIO-ICUNCT06473415

Electroencephalography and Sleep Quality With Lormetazepam in the Intensive Care Unit

An observational study of Critical Illness and Delirium, run by Charite University, Berlin, Germany at 1 site in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The goal of this clinical trial is to test the effect of continuous lormetazepam infusion on EEG patterns in critically ill patients who are given continuous infusion of lormetazepam in an intensive care unit setting. Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
Electroencephalography
How many people
50 participants
Where
1 siteGermany
Study dates
1 Dec 2023to 31 Dec 2024
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 100 years
  • All sexes
  • Adult, Older adult

Study population: 50 male and female critically ill patients aged 18 years or older

Who may be able to join

  • Patient capable of giving consent or additional legal guardian/authorized representative/spouse available for non-consenting patient in the intensive care unit
  • An expected continuous lormetazepam therapy ≥ 24 hours
  • Male and female patients aged ≥18 years
  • Expected duration of intensive care treatment ≥ 48 hours
  • Mechanical ventilation (invasive, NIV and/or nasal high-flow > 6h)

Who cannot join

  • Laboratory evidence of sedative/opiate intoxication
  • Active alcohol abuse
  • Brain surgery, cranial malformation
  • History of sleep-related movement disorder (symptomatic restless legs syndrome)
  • Allergy to electrode contact material
  • History of severe cognitive impairment following a stroke
Show all 16Show fewer
  • Status post cardiopulmonary resuscitation requiring/undergoing therapeutic hypothermia
  • Lack of consent for the pseudonymized disease data to be stored and passed on in the context of this clinical study
  • Patient is housed in an institution on court or official order
  • History of sleep-related breathing disorder
  • Suspicion of hypoxic brain damage (including intracranial hemorrhages)
  • Suspicion of increased intracranial pressure
  • Existing power of attorney or patient's will, in which the patient fundamentally excludes participation in studies
  • The patient's consent or that of the legal representative cannot be obtained in a timely manner
  • Patients with a survival probability < 24h
  • Narcolepsy

Trial locations and contacts

1 site in 1 country.

Alawi Luetz, Prof.Dr.med contact

+4930450631208

alawi.luetz@charite.de

Germany1 site, 1 recruiting
  • Charité - Universitätsmedizin Berlin

    Mitte, State of Berlin, 10117

    Alawi Luetz, MD

    Recruiting

Other trials in Germany

About this study

The goal of this clinical trial is to test the effect of continuous lormetazepam infusion on EEG patterns in critically ill patients who are given continuous infusion of lormetazepam in an intensive care unit setting. The main questions it aims to answer are:

  • How does the continuous infusion of lormetazepam affect EEG readings in terms of specific patterns related to sleep quality and sedation depth?
Read more

Participants will be asked to:

  • Receive continuous infusion of lormetazepam, administered as per the guidelines and judgment of the on-duty ward physician.
  • Undergo up to three EEG measurements over a period of 24 hours each using the X8 Sleep Profiler RTA device. These measurements will monitor brain activity and other related signals in order to assess the sedation depth and sleep quality.
  • These EEG readings will be performed after at least two hours of initiation of continuous lormetazepam infusion, potentially at different stages of their ICU stay.

There is no direct comparison group in this study. However, after initial data from the first 15 patients is collected, an interim analysis will be performed. This will help researchers understand the ability to measure sleep quality and defined EEG parameters in this setup, and if necessary, adapt the study design or measurement procedures for better outcomes.

Read the detailed description

The misadjusted use of sedatives in critically ill patients, especially the state of deep sedation stages, is associated with an increased occurrence of delirium and increased hospital mortality. Drug sedation should be avoided according to current recommendations of care guidelines and should only be used in symptom-oriented therapy. However, the administration of drugs with a sedative effect profile remains necessary not only for patients for brain pressure therapy or positioning maneuvers in severe lung failure, but is often necessary to achieve a patient who is awake and at the same time stress-free. A variety of drugs from different substance classes are available for this. Given that a large proportion of intensive care patients develop an acute substantial disruption of the circadian rhythm, which very often goes hand in hand with pathological sleep and delirium, sedatives, which are often given continuously over a longer period, should support good sleep quality and the physiological sleep-wake rhythm. However, studies show that commonly used sedatives such as propofol worsen sleep quality. Especially for the group of benzodiazepines, there are indications from several studies that the application, even compared to α2-agonists such as dexmedetomidine, significantly favors the risk of delirium. Lormetazepam for intravenous use has only been approved for continuous use in intensive care patients for a few years. Initial studies document very good anxiolysis and the avoidance of over-sedation compared to midazolam. Currently, there are no published works that have systematically investigated the effects of continuous lormetazepam infusion on the EEG and sleep quality in intensive care patients. However, these data are necessary in order to take sleep quality and neuroprotection into account when selecting and dosing sedatives in the future and to avoid chronodisruption and cognitive damage. Studies from dementia research but also a few from intensive care medicine provide indications for potentially brain-protective EEG patterns, which promote the glymphatic clearance of the cerebrospinal fluid. This includes not only primarily sleep-associated characteristics such as Slow Wave Sleep (SWS) and spindle activity but also frontal gamma oscillations, which can have memory-consolidating effects. Corresponding patterns are to be investigated in this pilot study under continuous lormetazepam infusion. The study involves further investigations according to primary and secondary endpoints, including EEG measurements. These EEG measurements are already part of the current care guidelines, but have not yet been comprehensively implemented in the ICU. The objective is to use EEG measurements in the future for more precise monitoring of the sedation depth of critically ill patients. Implementing this in the study may potentially allow for more adequate sedation management by being able to immediately respond to specific EEG patterns (e.g., burst-suppression) with an adjustment of sedation.

Given the described data situation, this is initially an exploratory pilot study.

The main Hypothesis: Intensive care patients who receive a continuous lormetazepam infusion exhibit an electroencephalographically detectable REM portion of at least 20%.

The EEG measurements are carried out up to three times over 24 hours using the X8 Sleep Profiler RTA (Advanced Brain Monitoring). It is a single-channel EEG measuring device that captures up to five channels of electrophysiological signals with just three electrodes, a photoplethysmographic (PPG) signal, and detects noise as well as movement and position. The X8 system can record and store data in its internal memory. The Sleep Profiler RTA software offers a visual display of the recordings in near real-time.

The study plans to enroll 50 patients in a prospective pilot study at the Charité Mitte Campus 101i ICU ward. It will include ICU patients expected to require intensive treatment for 48 hours or longer and an expected continuous lormetazepam infusion of at least 24 hours. The indications and duration of intravenous lormetazepam therapy will be determined by the on-duty ward physician in accordance with the internal clinic standards. Episodic EEG measurements will be conducted. The patient screening takes place immediately after admission to the ICU and will be reevaluated every day for meeting inclusion criteria.

The EEG recordings will be made in periods of 24 hours and will start at least two hours after the initiation of the continuous lormetazepam infusion. An EEG-P is only considered complete if the measurement within the core measurement time was not interrupted.

Being tested
Electroencephalography
Medical subject headings
Critical Illness, Delirium, Sleep Disorders, Circadian Rhythm

What participants receive

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

  • ElectroencephalographyDiagnostic test

    Electroencephalography using the Sleep-Profiler device

What is being measured

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

  1. REM portion (%) during nocturnal sleep

    Main Hypothesis: Intensive care patients who receive a continuous Lormetazepam infusion exhibit an electroencephalographically detectable REM portion of at least 20% during the nocturnal sleeping period bewetween 22:00 to 06:00.

    Measured: through study completion per patient, an average of 3 days

Secondary outcomes (50)
  1. Total sleep time attributed to stages N2, N3 or rapid eye movement (REM) sleep during the noctural period i.e., between the hours of 22:00 and 06:00

    Total high qualitiy sleep time during nocturnal period, (sum REM,N2,N3; minutes)

    Measured: through study completion per patient, an average of 3 days

  2. Total minutes of all stages of sleep (including N1, AN3, NREM hypertonia) during the awake period i.e., between the hours of 06:00 and 22:00.

    Total sleep time during awake period, (minutes)

    Measured: through study completion per patient, an average of 3 days

  3. Total and % time atypical N3 sleep (AN3) i.e. polymorphic delta or or sepsis associated encephalopathy

    Total sleep time in atypical N3 (minutes; %)

    Measured: through study completion per patient, an average of 3 days

  4. Gamma oscillations

    Hz)

    Measured: through study completion per patient, an average of 3 days

  5. Theta-Gamma Coupling

    (TGC, Modulation Index)

    Measured: through study completion per patient, an average of 3 days

  6. Polymorphic Delta/Theta Ratio

    (DTR, %)

    Measured: through study completion per patient, an average of 3 days

  7. Slow Wave Sleep (SWS) Characteristics

    This outcome measure will aggregate the characteristics of Slow Wave Sleep (SWS) by reporting the total duration (in minutes) and the average frequency (in Hz) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of SWS.

    Measured: through study completion per patient, an average of 3 days

  8. Pathological N3-Slow Wave Sleep Characteristics

    This outcome measure will aggregate the characteristics of Pathological N3-Slow Wave Sleep by reporting the total duration (in minutes) and the average frequency (in Hz) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of N3-Slow Wave Sleep.

    Measured: through study completion per patient, an average of 3 days

  9. Sleep Spindle Characteristics

    This outcome measure will aggregate the characteristics of sleep spindles by reporting the total occurrence (number per minute/hour), average frequency (in Hz), and total duration (in minutes) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of sleep spindles.

    Measured: through study completion per patient, an average of 3 days

  10. Pseudo Spindle Characteristics supression and/or medications

    This outcome measure will aggregate the characteristics of pseudo spindles by reporting the total duration (in minutes attributed to burst suppression and/or medications), average frequency (in Hz), and total occurrence (number per minute/hour) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of pseudo spindles.

    Measured: through study completion per patient, an average of 3 days

  11. K-Complex Characteristics

    This outcome measure will aggregate the characteristics of K-complexes by reporting the total occurrence (number per minute/hour) and average frequency (in Hz) during each measurement period. The aggregated value will combine these measurements to provide a comprehensive assessment of K-complexes.

    Measured: through study completion per patient, an average of 3 days

  12. Burst-Suppression

    (Supression Index,%)

    Measured: through study completion per patient, an average of 3 days

  13. Total sleep time

    (minutes)

    Measured: through study completion per patient, an average of 3 days

  14. Sleep latency

    (SOL, minutes)

    Measured: through study completion per patient, an average of 3 days

  15. Nocturnal sleep efficiency (%)

    (Total sleep duration/8 hours) x 100

    Measured: through study completion per patient, an average of 3 days

  16. Eye movements during sleep

    (number)

    Measured: through study completion per patient, an average of 3 days

  17. REM latency

    (minutes)

    Measured: through study completion per patient, an average of 3 days

  18. REM-Sleep-Pressure-Index

    (RSPI, %)

    Measured: through study completion per patient, an average of 3 days

  19. Delirium incidence in intensive care unit measured with the Confusion Assessment Method

    CAM-ICU

    Measured: through study completion per patient, an average of 3 days

  20. Delirium severity in intensive care unit measured with the Intensive Care Delirium Screening Checklist

    (ICDSC)

    Measured: through study completion per patient, an average of 3 days

  21. Sedation depth: Richmond Agitation Sedation Scale

    The Richmond Agitation Sedation Scale (RASS) ranges from -5 to +4, with lower scores indicating deeper sedation and higher scores indicating greater agitation. The scale includes +4 (combative), +3 (very agitated), +2 (agitated), +1 (restless), 0 (alert and calm), -1 (drowsy), -2 (light sedation), -3 (moderate sedation), -4 (deep sedation), and -5 (unarousable). Higher scores indicate worse outcomes in terms of agitation(RASS)

    Measured: through study completion per patient, an average of 3 days

  22. Analgesia level: Numeric Rating Scale Visualized (NRS-V) or Faces Pain Scale Revised (FAS-R) Behavioural Pain Scale (BPS) or Behavioural Pain Scale for non-intubated patients (BPS-NI)

    The analgesia level will be assessed using the Numeric Rating Scale Visualized (NRS-V), Faces Pain Scale Revised (FAS-R), Behavioural Pain Scale (BPS), or Behavioural Pain Scale for non-intubated patients (BPS-NI). The NRS-V ranges from 0 (no pain) to 10 (worst pain imaginable). The FAS-R uses facial expressions to represent pain levels from 0 (no pain) to 10 (worst pain imaginable). The BPS scores range from 3 (no pain) to 12 (severe pain) based on facial expression, upper limb movements, and compliance with ventilation. The BPS-NI scores range from 3 (no pain) to 12 (severe pain) based on facial expression, upper limb movements, and vocalization. Higher scores indicate worse pain outcomes.

    Measured: through study completion per patient, an average of 3 days

  23. Total amount of intravenously administered opioids per ICU treatment day

    type, cumulative dose

    Measured: through study completion per patient, an average of 3 days

  24. Total amount of administered neuroleptics per ICU treatment day

    type, cumulative dose

    Measured: through study completion per patient, an average of 3 days

  25. Duration of invasive and non-invasive ventilation

    intubated, nasal highflow, NIV-mask

    Measured: through study completion per patient, an average of 3 days

  26. Intensive care duration at the center

    days

    Measured: through study completion, an average of 1 year

  27. Hospital treatment duration at the center

    days

    Measured: through study completion, an average of 1 year

  28. Sepsis/Septic Shock

    Sepsis/Septic Shock

    Measured: through study completion per patient, an average of 3 days

  29. Sequential Organ Failure Assessment

    The Sequential Organ Failure Assessment (SOFA) Score assesses organ function and predicts outcomes in critically ill patients. The score ranges from 0 to 24, with higher scores indicating greater organ dysfunction. It evaluates six organ systems: respiratory, cardiovascular, hepatic, coagulation, renal, and neurological. Each system is scored from 0 (normal function) to 4 (high degree of dysfunction). Higher SOFA scores are associated with worse patient outcomes (SOFA).

    Measured: through study completion per patient, an average of 3 days

  30. Simplified Acute Physiology Score

    The Simplified Acute Physiology Score II (SAPS II) is used to assess the severity of disease for patients admitted to intensive care units. The score ranges from 0 to 163, with higher scores indicating a higher risk of mortality. SAPS II includes 17 variables: 12 physiological variables, age, type of admission (scheduled surgical, unscheduled surgical, medical), and three underlying disease variables (AIDS, hematologic malignancy, metastatic cancer). Higher SAPS II scores correspond to worse patient outcomes (SAPSII).

    Measured: through study completion per patient, an average of 3 days

  31. Therapeutic Intervention Scoring System

    The Therapeutic Intervention Scoring System (TISS) measures the intensity of medical and nursing care required by ICU patients. The score ranges from 0 to 78, with higher scores indicating more intensive care. TISS evaluates various therapeutic interventions, including cardiovascular, renal, respiratory, and neurological support, as well as monitoring, medication, and hygiene procedures. Higher TISS scores reflect a greater need for medical and nursing interventions (TISS).

    Measured: through study completion per patient, an average of 3 days

  32. Acute Physiological And Chronic Health Evaluation

    The Acute Physiology and Chronic Health Evaluation II (APACHE II) score is used to measure the severity of disease in ICU patients. The score ranges from 0 to 71, with higher scores indicating more severe disease and higher risk of mortality. APACHE II includes the evaluation of 12 physiological variables, age, and chronic health status. Higher APACHE II scores are associated with worse patient outcomes (APACHE II).

    Measured: through study completion per patient, an average of 3 days

  33. Age

    (years)

    Measured: through study completion per patient, an average of 3 days

  34. Gender

    (m/f/d)

    Measured: through study completion per patient, an average of 3 days

  35. Fever

    yes/no, days)

    Measured: through study completion per patient, an average of 3 days

  36. Respiratory insufficiency/Asthma (yes/no)

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  37. Cardiac arrest/Cardiac decompensation

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  38. Pneumonia

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  39. Urinary tract infection

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  40. Exacerbated COPD

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  41. Hypervolemia

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  42. Meningitis

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  43. Pancreatitis

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  44. Cirrhosis

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  45. Kidney insufficiency

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  46. Thrombocytopenia

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  47. Leukocytosis

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  48. Leukopenia

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  49. Hypotonia

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

  50. Death

    (yes/no)

    Measured: through study completion per patient, an average of 3 days

Timeline

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

  1. First posted25 Jun 2024
  2. Study start1 Dec 2023
  3. Primary completion1 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

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
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06473415
Sponsor's protocol ID
20019702
Acronym
CLIO-ICU
Status last verified
Jun 2024
First submitted
12 Jun 2024
Last updated
26 Jun 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

An observational study of Critical Illness and Delirium, run by Charite University, Berlin, Germany at 1 site in Germany.

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 16 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 26 Jun 2024. 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 Germany. 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 Alawi Luetz, Prof.Dr.med (+4930450631208, alawi.luetz@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

REM portion (%) during nocturnal sleep (time frame: through study completion per patient, an average of 3 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 26 Jun 2024.

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