Sepsis-Associated EncephalopathyADVISENCT04076826
Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy
A study testing Dexmedetomidine, Propofol or Midazolam and Blood sampling in people with Sepsis-Associated Encephalopathy, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
Septic encephalopathy (SE) is defined as acute cerebral dysfunction in patients with sepsis or septic shock. SE occurs in up to 50% of critically ill patients with sepsis and is associated with a high mortality and morbidity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis-Associated Encephalopathy
- What is being tested?
- Dexmedetomidine, Propofol or Midazolam and Blood sampling
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Sep 2019to 8 Jul 2022
- 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
- The participant is aged 18 years or older
- The participant has been intubated and is receiving mechanical ventilation
- The participant requires sedative medication for comfort, safety or to facilitate the delivery of life support measures
- The participant has either a central venous or an arterial catheter inserted within 24 hours of admission
- The participant has a diagnosis of sepsis based on the recent SEPSIS-3 consensus clinical criteria.
Who cannot join
- Age < 18 years
- The treating physician believes that the participant will remain intubated for <24 hours or the participant has been intubated for diagnostic or therapeutic procedures as the sole reason for mechanical ventilation.
- Participants with any of the following admission diagnosis: acute cerebral vascular event, traumatic brain injury, epilepsy, hypoxic brain injury, meningitis, encephalitis
- Participants with history of melanoma (S 100-β is elevated in melanoma participants)
- Participants with schizophrenia or other chronic psychiatric conditions
- Admission for drug overdose
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- Planned administration of ongoing neuromuscular blockade
- Heart rate < 55 / min or an atrioventricular block > grade 2a in the absence of a functioning pacemaker
- Known hypersensitivity or allergy to any of the sedative medications used in this study.
- DNR (do not resuscitate) or DNI (do not intubate) orders
- Death is deemed to be imminent or inevitable during this admission and either the attending physician, participant or substitute decision maker is not committed to active treatment
- Women who are pregnant or breast feeding
- Known or suspected non-compliance, drug or severe alcohol abuse
- Inability of the participant to understand the procedures of the study, e.g. due to language problems, psychological disorders, or dementia
- Previous enrolment into the current study
- Enrolment of the investigator, his/her family members, employees and other dependent persons
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy: a Pilot Randomized Controlled Study.
Septic encephalopathy (SE) is defined as acute cerebral dysfunction in patients with sepsis or septic shock. SE occurs in up to 50% of critically ill patients with sepsis and is associated with a high mortality and morbidity. The pathophysiology of SE is complex and involves increased levels of inflammatory mediators such as tumor necrosis factor (TNF)-α, Interleukin (IL)-1 and IL-6, leading to blood brain barrier dysfunction and neuronal inflammation. Several biomarkers of neuronal injury have been proposed to identify patients with SE. Of these biomarkers, S100-β has the highest sensitivity and specificity.
Sedation with Dexmedetomidine (DEX) is a promising strategy for the management of these patients, as DEX has been shown to decrease the production of inflammatory mediators in experimental models of sepsis. In clinical studies, DEX lowers the incidence of delirium and critical illness polyneuropathy. However, its effectiveness in treatment and prevention of SE remains unclear.
The aim of the present study is to investigate the effect of two standard sedation protocols (Dexmedetomidine sedation vs. Propofol / Midazolam) on serum markers of SE in critically ill patients with sepsis who require sedation and mechanical ventilation.
- Conditions
- Sepsis-Associated Encephalopathy
- Being tested
- Dexmedetomidine, Propofol or Midazolam, Blood sampling
- Keywords
- Sepsis, Dexmedetomidine, Sedation, S-100beta, Encephalopathy
- Medical subject headings
- Sepsis-Associated Encephalopathy, Sepsis, Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Protocol A
Dexmedetomidine infusion will be commenced in accordance with the hospital's local sedation protocol, without a loading dose, at a rate of 0.1 - 1.4 mcg/kg/hour to maintain sedation as per Richmond Agitation-Sedation Scale (RASS) sedation range specified by the treating clinician. Infusion will be continued until sedation is no longer clinically indicated up to a maximum of 7 days after enrolment.
Propofol or MidazolamDrug
Also called Protocol B
Propofol and/or Midazolam will be used according to Hospital guidelines to maintain sedation as per Richmond Agitation-Sedation Scale (RASS) sedation range specified by the treating clinician.
Blood samplingDiagnostic test
In all participants, we will collect blood samples for measurement of neuronal and systemic biomarkers of inflammation at randomization (baseline), at day 1, day 2 and day 3 after randomization.
| Study group | Role | What they receive |
|---|---|---|
| Protocol A (Dexmedetomidine) | Experimental | Dexmedetomidine will be administered in accordance with hospital standard operating procedures (SOP). Receives: Drug: Dexmedetomidine; Diagnostic Test: Blood sampling |
| Protocol B (Propofol / Midazolam) | Active comparator | Propofol and/or Midazolam will be administered in accordance with hospital standard operating procedures (SOP). Receives: Drug: Propofol or Midazolam; Diagnostic Test: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
S100-ß
Serum concentration of S100-ß
Measured: at 48 hours after randomization
Secondary outcomes (6)
Neuron-specific enolase
Serum concentration of Neuron-specific enolase
Measured: first 3 days after randomization
Interleukin 1-beta
Serum concentration of Interleukin 1-beta
Measured: first 3 days after randomization
Interleukin 6
Serum concentration of Interleukin 6
Measured: first 3 days after randomization
TNF alpha
Serum concentration of TNF alpha
Measured: first 3 days after randomization
Acetylcholinesterase activity
Acetylcholinesterase activity will be measured using a point-of-care device and reported as Units/grams Haemoglobin
Measured: first 3 days after randomization
Butyrylcholinesterase activity
Butyrylcholinesterase activity will be measured using a point-of-care device and reported as Units/L
Measured: first 3 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2019
- Study start1 Sep 2019
- Primary completion17 Jun 2022
- Study completion8 Jul 2022
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 Sepsis-Associated EncephalopathyStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luca Cioccari, Insel Gruppe AG, University Hospital Bern
- Investigators
- Luca Cioccari, MD, Principal investigator, Insel Gruppe AG, University Hospital Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04076826
- Sponsor's protocol ID
- 4051
- Acronym
- ADVISE
- Status last verified
- Feb 2023
- First submitted
- 22 Aug 2019
- Last updated
- 13 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Iten M, Bachmann K, Jakob SM, Grandgirard D, Leib SL, Cioccari L. Adjunctive Sedation with Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy: A Pilot Randomized Controlled Study. Crit Care Med. 2025 Jul 1;53(7):e1377-e1388. doi: 10.1097/CCM.0000000000006655. Epub 2025 Mar 31.
PubMed 40162868
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy: a Pilot Randomized Controlled Study.
- ClinicalTrials.gov ID
- NCT04076826
- Acronym / sponsor ID
- ADVISE / 4051
- Conditions
- Sepsis-Associated Encephalopathy
- Keywords
- Sepsis, Dexmedetomidine, Sedation, S-100beta, Encephalopathy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 17 Jun 2022 (actual)
- Study completion
- 8 Jul 2022 (actual)
- First posted
- 3 Sep 2019 (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.
Septic encephalopathy (SE) is defined as acute cerebral dysfunction in patients with sepsis or septic shock. SE occurs in up to 50% of critically ill patients with sepsis and is associated with a high mortality and morbidity. The pathophysiology of SE is complex and involves increased levels of inflammatory mediators such as tumor necrosis factor (TNF)-α, Interleukin (IL)-1 and IL-6, leading to blood brain barrier dysfunction and neuronal inflammation. Several biomarkers of neuronal injury have been proposed to identify patients with SE. Of these biomarkers, S100-β has the highest sensitivity and specificity.
Sedation with Dexmedetomidine (DEX) is a promising strategy for the management of these patients, as DEX has been shown to decrease the production of inflammatory mediators in experimental models of sepsis. In clinical studies, DEX lowers the incidence of delirium and critical illness polyneuropathy. However, its effectiveness in treatment and prevention of SE remains unclear.
The aim of the present study is to investigate the effect of two standard sedation protocols (Dexmedetomidine sedation vs. Propofol / Midazolam) on serum markers of SE in critically ill patients with sepsis who require sedation and mechanical ventilation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Protocol A (Dexmedetomidine) | Experimental | Drug: Dexmedetomidine, Diagnostic Test: Blood samplingDexmedetomidine will be administered in accordance with hospital standard operating procedures (SOP). |
| Protocol B (Propofol / Midazolam) | Active comparator | Drug: Propofol or Midazolam, Diagnostic Test: Blood samplingPropofol and/or Midazolam will be administered in accordance with hospital standard operating procedures (SOP). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- The participant is aged 18 years or older
- The participant has been intubated and is receiving mechanical ventilation
- The participant requires sedative medication for comfort, safety or to facilitate the delivery of life support measures
- The participant has either a central venous or an arterial catheter inserted within 24 hours of admission
- The participant has a diagnosis of sepsis based on the recent SEPSIS-3 consensus clinical criteria.
Key exclusion criteria (16 listed)
- Age < 18 years
- The treating physician believes that the participant will remain intubated for <24 hours or the participant has been intubated for diagnostic or therapeutic procedures as the sole reason for mechanical ventilation.
- Participants with any of the following admission diagnosis: acute cerebral vascular event, traumatic brain injury, epilepsy, hypoxic brain injury, meningitis, encephalitis
- Participants with history of melanoma (S 100-β is elevated in melanoma participants)
- Participants with schizophrenia or other chronic psychiatric conditions
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 |
|---|---|---|
| DexmedetomidineAlso: Protocol ADexmedetomidine infusion will be commenced in accordance with the hospital's local sedation protocol, without a loading dose, at a rate of 0.1 - 1.4 mcg/kg/hour to maintain sedation as per Richmond Agitation-Sedation Scale (RASS) sedation range specified by the treating clinician. Infusion will be continued until sedation is no longer clinically indicated up to a maximum of 7 days after enrolment. | Drug | Protocol A (Dexmedetomidine) |
| Propofol or MidazolamAlso: Protocol BPropofol and/or Midazolam will be used according to Hospital guidelines to maintain sedation as per Richmond Agitation-Sedation Scale (RASS) sedation range specified by the treating clinician. | Drug | Protocol B (Propofol / Midazolam) |
| Blood samplingIn all participants, we will collect blood samples for measurement of neuronal and systemic biomarkers of inflammation at randomization (baseline), at day 1, day 2 and day 3 after randomization. | Diagnostic test | Protocol A (Dexmedetomidine), Protocol B (Propofol / Midazolam) |
Primary outcome
S100-ß
Time frame: at 48 hours after randomization
Serum concentration of S100-ß
6 secondary outcomes
Neuron-specific enolase
Time frame: first 3 days after randomization
Interleukin 1-beta
Time frame: first 3 days after randomization
Interleukin 6
Time frame: first 3 days after randomization
TNF alpha
Time frame: first 3 days after randomization
Acetylcholinesterase activity
Time frame: first 3 days after randomization
Butyrylcholinesterase activity
Time frame: first 3 days after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2023.
- Derived from this study: PubMed 40162868Iten M, Bachmann K, Jakob SM, Grandgirard D, Leib SL, Cioccari L. Adjunctive Sedation with Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy: A Pilot Randomized Controlled Study. Crit Care Med. 2025 Jul 1;53(7):e1377-e1388. doi: 10.1097/CCM.0000000000006655. Epub 2025 Mar 31.
- Individual participant dataSharing planned: No
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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.
Luca Cioccari, MD principal investigator
Insel Gruppe AG, University Hospital Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dexmedetomidine, Propofol or Midazolam and Blood sampling in people with Sepsis-Associated Encephalopathy, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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: finished, as of the sponsor's last update on 13 Feb 2023. 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 Switzerland. 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?
S100-ß (time frame: at 48 hours after randomization). 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 NCT04076826, 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 13 Feb 2023.