Mechanistic Inflammatory Sub-study Embedded Within the Albumin vs Balanced Crystalloid Trial (MIS-ABC Sepsis)

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.

Study Overview

• Status: Completed
• Conditions: Sepsis

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.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• United Kingdom
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH16 4SA
      • Royal Infirmary of Edinburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals presenting to the Emergency Department, Acute Medical Unit or Surgical Admission Unit.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Albumin; Participants enrolled in the ABC Sepsis trial who have been randomised to 5% Human Albumin Solution as the sole resuscitative fluid in the first 6 hours.
Balanced Crystalloid; Participants enrolled in the ABC Sepsis trial who have been randomised to Balanced Crystalloid as the sole resuscitative fluid in the first 6 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis.	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.	At presentation, 12 and 24 hours.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. TNF-alpha at Presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. TNF-alpha at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. TNF-alpha at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. GM-CSF at Presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. GM-CSF at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. GM-CSF at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-6 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-6 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-6 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL10 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL10 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL10 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation.
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. Il-5 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. Il-5 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. Il-5 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-a2 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-a2 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-a2 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-4 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-4 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-4 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL3 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL3 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-10 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-10 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-10 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-12p70 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-12p70 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IL-12p70 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from baseline
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL20 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from baseline
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL20 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL20 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-gamma at Presentation	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-gamma at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. IFN-gamma at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL8 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL8 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CXCL8 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	24 hours from baseline
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL4 at 0 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	0 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL4 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at presentation.	12 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL4 at 24 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 24 hours.	24 hours from presentation
Longitudinal Change Over Time in Cell Types and Pro and Anti Inflammatory Cytokines in Sepsis. CCL3 at 12 Hours	Exploratory analysis to map mechanistic inflammatory response. Comparison of mean cytokine concentrations between allocation arms. Comparing at 12 hours from presentation.	12 hours from presentation

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: NHS Lothian; Royal College of Emergency Medicine
• Investigators: Study Director: Alasdair Gray, MD, University of Edinburgh

Publications and helpful links

Helpful Links

• ABC Sepsis Trial Registration
• Study Webpage

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Actual): June 8, 2022
• Study Completion (Actual): June 8, 2022

Study Registration Dates

• First Submitted: June 10, 2021
• First Submitted That Met QC Criteria: July 5, 2021
• First Posted (Actual): July 15, 2021

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 4, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: infection; albumin; inflammation; fluids; sepsis; cytokine; intravenous; crystalloid; resuscitation; interleukin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis
• Other Study ID Numbers: AC21050; G/2021/1 (Other Grant/Funding Number: Royal College of Emergency Medicine); 301333 (Other Identifier: IRAS (England)); 300332 (Other Identifier: IRAS (Scotland))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We plan to share study day according to the FAIR principles, after agreement with the study sponsor policies.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No