Clinical trial NCT04963569: Mechanistic Inflammatory Sub-study Embedded Within the Albumin vs Balanced Crystalloid Trial
Official title: Mechanistic Inflammatory Sub-study Embedded Within the Albumin vs Balanced Crystalloid Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Keywords: sepsis
infection
inflammation
cytokine
interleukin
intravenous
fluids
resuscitation
albumin
crystalloid
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: NHS Lothian
name: Royal College of Emergency Medicine
First posted: 2021-07-15
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals presenting to the Emergency Department, Acute Medical Unit or Surgical Admission Unit.

Brief summary: MIS-ABC Sepsis is a sub-study looking to understand how the immune response in patients with infection changes during the early stages of the illness, as well as after intravenous fluid treatment. Participants in the main trial will be given one of two types of fluid (Human Albumin Solution (HAS) and Balanced Crystalloid) via a drip when they present to the hospital with severe infection (sepsis). The main trial is assessing which fluid is better, and we are going to take three blood samples around the time people come to hospital to see what happens to their immune system as a result of the infection and fluid treatment. We hope our findings will explain why one fluid might be better than another. It may also give us an important information about whether we can predict which people might get sicker despite treatment.

Detailed description: MIS-ABC Sepsis is linked to the ABC-Sepsis trial, a pilot feasibility trial recruiting patients with community acquired infection/sepsis with a NEWS2 score of five or more and randomising the participants to receiving either balanced crystalloid or 5% HAS as the intravenous resuscitation fluid up to six hours after randomisation.

MIS-ABC Sepsis will take serial blood samples from a small number of these participants, at hospital presentation and at two further points early during the patient's admission, to allow analysis of how inflammation changes during their course of illness. Investigating temporal change and differences between treatment arms of the main study will allow a nuanced analysis of the interplay between severity of illness, physiological changes over time and any potential differences between fluid treatment arm.

This is a prospective observational study enrolling patients randomised to the ABC Sepsis study. Centres for this trial will be selected from UK NHS hospitals who are recruiting to the main ABC Sepsis study. Participants will be recruited as soon as possible, and up to 12 hours after presentation to the Emergency Department, Surgical Assessment Unit or Medical Admissions Unit.

The treatment phase of the main study spans 6 hours following randomisation, with the follow up period extending to 90 days. This sub-study requires three blood samples: immediately after enrolment, at approximately 12 and 24 hours thereafter. The follow up period similarly extends to 90 days, using routine data from the medical records for follow up.

Eligibility criteria: Inclusion Criteria:

* Able to obtain informed consent
* Eligible for and randomised into the ABC Sepsis trial

Exclusion Criteria:

* Excluded from the ABC Sepsis trial

Primary outcomes:
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis.
timeFrame: At presentation, 12 and 24 hours.
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. TNF-alpha at Presentation
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. TNF-alpha at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. TNF-alpha at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. GM-CSF at Presentation
timeFrame: 0 hours
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. GM-CSF at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. GM-CSF at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-6 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-6 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-6 at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL10 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL10 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL10 at 24 Hours
timeFrame: 24 hours from presentation.
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. Il-5 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. Il-5 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. Il-5 at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-a2 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-a2 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-a2 at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-4 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-4 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-4 at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL3 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL3 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL3 at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-10 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-10 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-10 at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-12p70 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-12p70 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-12p70 at 24 Hours
timeFrame: 24 hours from baseline
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL20 at 0 Hours
timeFrame: 0 hours from baseline
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL20 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL20 at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-gamma at Presentation
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-gamma at 0 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-gamma at 24 Hours
timeFrame: 24 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL8 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL8 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL8 at 24 Hours
timeFrame: 24 hours from baseline
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL4 at 0 Hours
timeFrame: 0 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL4 at 12 Hours
timeFrame: 12 hours from presentation
measure: Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL4 at 24 Hours
timeFrame: 24 hours from presentation
Secondary outcomes:
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: Midlothian
Study officials:
affiliation: University of Edinburgh
name: Alasdair Gray, MD
role: STUDY_DIRECTOR
References: