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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Sepsis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to obtain informed consent Eligible for and randomised into the ABC Sepsis trial Exclusion Criteria: Excluded from the ABC Sepsis trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Albumin<br>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<br>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?
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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. | At presentation, 12 and 24 hours. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, infection, inflammation, cytokine, interleukin, intravenous, fluids, resuscitation, albumin, crystalloid