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Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy (ADVISE)

Primary Purpose

Sepsis-Associated Encephalopathy

Status

Completed

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

Dexmedetomidine

Propofol or Midazolam

Blood sampling

About this trial

This is an interventional prevention trial for Sepsis-Associated Encephalopathy focused on measuring Sepsis, Dexmedetomidine, Sedation, S-100beta, Encephalopathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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
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

Sites / Locations

Inselspital, Bern University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Protocol A (Dexmedetomidine)

Protocol B (Propofol / Midazolam)

Arm Description

Dexmedetomidine will be administered in accordance with hospital standard operating procedures (SOP).

Propofol and/or Midazolam will be administered in accordance with hospital standard operating procedures (SOP).

Outcomes

Primary Outcome Measures

S100-ß

Serum concentration of S100-ß

Secondary Outcome Measures

Neuron-specific enolase

Serum concentration of Neuron-specific enolase

Interleukin 1-beta

Serum concentration of Interleukin 1-beta

Interleukin 6

Serum concentration of Interleukin 6

TNF alpha

Serum concentration of TNF alpha

Acetylcholinesterase activity

Acetylcholinesterase activity will be measured using a point-of-care device and reported as Units/grams Haemoglobin

Butyrylcholinesterase activity

Butyrylcholinesterase activity will be measured using a point-of-care device and reported as Units/L

Full Information

NCT ID

NCT04076826

First Posted

August 22, 2019

Last Updated

February 10, 2023

Sponsor

Insel Gruppe AG, University Hospital Bern

1. Study Identification

Unique Protocol Identification Number

NCT04076826

Brief Title

Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy

Acronym

ADVISE

Official Title

Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy: a Pilot Randomized Controlled Study.

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

September 1, 2019 (Actual)

Primary Completion Date

June 17, 2022 (Actual)

Study Completion Date

July 8, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Insel Gruppe AG, University Hospital Bern

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sepsis-Associated Encephalopathy

Keywords

Sepsis, Dexmedetomidine, Sedation, S-100beta, Encephalopathy

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Protocol A (Dexmedetomidine)

Arm Type

Experimental

Arm Description

Dexmedetomidine will be administered in accordance with hospital standard operating procedures (SOP).

Arm Title

Protocol B (Propofol / Midazolam)

Arm Type

Active Comparator

Arm Description

Propofol and/or Midazolam will be administered in accordance with hospital standard operating procedures (SOP).

Intervention Type

Drug

Intervention Name(s)

Dexmedetomidine

Other Intervention Name(s)

Protocol A

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Propofol or Midazolam

Other Intervention Name(s)

Protocol B

Intervention Description

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.

Intervention Type

Diagnostic Test

Intervention Name(s)

Blood sampling

Intervention Description

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.

Primary Outcome Measure Information:

Title

S100-ß

Description

Serum concentration of S100-ß

Time Frame

at 48 hours after randomization

Secondary Outcome Measure Information:

Title

Neuron-specific enolase

Description

Serum concentration of Neuron-specific enolase

Time Frame