Mechanistic Inflammatory Sub-study Embedded Within the Albumin vs Balanced Crystalloid Trial

Completed

Conditions: Sepsis

Registration Number: NCT04963569

Lead Sponsor: University of Edinburgh

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 26

Inclusion Criteria

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

Exclusion Criteria

Excluded from the ABC Sepsis trial

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis.	At presentation, 12 and 24 hours.	Exploratory analysis to map mechanistic inflammatory response over time: 0, 12 and 24 hours. As the analysis is exploratory, there is no defined limit to cell types or cytokines measured. Cytokines measured: tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), C-X-C motif chemokine ligand 10 (CXCL10), interleukin 5 (IL-5), interferon alpha 2 (IFN-a2), interleukin 4 (IL-4), C-C motif chemokine ligand 3 (CCL3), interleukin 10 (IL-10), interleukin 12p70 (IL-12p70), C-C motif chemokine ligand 20 (CCL20), interferon gamma (IFN-gamma), C-X-C motif chemokine ligand 8 (CXCL8), and C-C motif chemokine 4(CCL4). This outcome measure describes the number of participants who were eligible for inclusion in the exploratory analysis described above and in later outcomes. Units: number of participants eligible for inclusion in comparison.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. TNF-alpha at Presentation	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. TNF-alpha at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. TNF-alpha at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. GM-CSF at Presentation	0 hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. GM-CSF at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. GM-CSF at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-6 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-6 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-6 at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL10 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL10 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL10 at 24 Hours	24 hours from presentation.	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. Il-5 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. Il-5 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. Il-5 at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-a2 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-a2 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-a2 at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-4 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-4 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-4 at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL3 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL3 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours from presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL3 at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-10 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-10 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-10 at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-12p70 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-12p70 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-12p70 at 24 Hours	24 hours from baseline	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL20 at 0 Hours	0 hours from baseline	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL20 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL20 at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-gamma at Presentation	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-gamma at 0 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-gamma at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL8 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL8 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL8 at 24 Hours	24 hours from baseline	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL4 at 0 Hours	0 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL4 at 12 Hours	12 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL4 at 24 Hours	24 hours from presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.