Early Detection of At-risk Septic Patients (MMICS)

An Observational Pilot Study for the Multi-Modality Risk Prediction and Early Identification of Critically Ill Septic Patients in the Emergency Department

The purpose of this study is to determine whether additional investigations used in other parts of healthcare can be used in the Emergency Department to identify critically ill patients quicker than usual care.

Study Overview

• Status: Recruiting
• Conditions: Sepsis
• Intervention / Treatment: Diagnostic test: Measuring tissue oxygenation; Diagnostic test: Procalcitonin; Diagnostic test: Mid-regional proadrenomedullin; Diagnostic test: Hand-held video microscope

Detailed Description

The investigators intend to recruit 56 patients with suspected sepsis who attend the Emergency Department. The investigators want to use a device to monitor tissue oxygen levels when they first come into the Emergency Department as well as the change in tissue oxygen levels when a tourniquet is applied for 3 minutes. The investigators will take novel blood tests when the patient is having their routine bloods. Finally, the investigators will use a special camera to take specialised pictures of the small blood vessels under the tongue which will show blood flow through these vessels. The investigators will follow the recruited patients and determine if our extra data is better at determining who needs critical care. A significant proportion of patients may be too unwell or too distressed to consent to be part of this study. At the earliest opportunity, the investigators will ask patients when they have been stabilised and are able to give consent. If they say no, they will be removed from the study and their care will not be affected by this decision.

The results could help us identify septic shock as early as possible so that these unwell patients are identified early and get the correct treatment they need. This could mean starting advanced treatments usually found in the Intensive Care Unit very early on in a patient's journey.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: James N Ward, BM; Phone Number: +447881967336; Email: wardj@doctors.org.uk
• Study Contact Backup: Name: Ahilanandan Dushianthan, PhD; Phone Number: +447903943418; Email: a.dushianthan@soton.ac.uk

Study Locations

• United Kingdom
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Recruiting
      • University Hospital Southampton NHS Foundation Trust
      • Contact: James N Ward, BM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients presenting to the Emergency Department with their illness possibly caused by sepsis

Description

Inclusion Criteria:

1. Differential diagnosis which includes infection
2. Change in the quick Sequential Organ Failure Assessment (qSOFA) ≥2 or National Early Warning Score 2 (NEWS2) score ≥5
3. Aged ≥18 years

Exclusion Criteria:

1. Traumatic injury
2. Rockwood frailty score ≥6
3. Critical care therapy previously believed to not be in patient's best interests

4. Critical care therapies-initiated pre-hospital. Critical care therapies defined as:

   4.1 Mechanical ventilation 4.2 Vasopressor/inotrope therapy 4.3 Sedation or a general anaesthetic 4.4 Pre-hospital transfusion of blood products 4.5 Extra-corporeal support

5. Advanced directive refusing critical care therapies.
6. Acute cardiac failure
7. Active gastrointestinal bleed
8. Massive pulmonary embolism
9. ICU admission declined by critical care team
10. Treated in an acute hospital <6 hours before presentation to the Emergency Department

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients presenting to the Emergency Department with suspected sepsis; Patients who present with potential sepsis. This is characterised by their illness suspected to be from an infection and significantly unwell defined by one of two scoring systems, either the National Early Warning Score or quick Sequential Organ Failure Assessment

Diagnostic test: Measuring tissue oxygenation; Measuring oxygen content of arteries, capillaries and veins; Diagnostic test: Procalcitonin; Blood test; Other Names: PCT; Diagnostic test: Mid-regional proadrenomedullin; Blood test looking at inflammation in the body; Other Names: MR-proADM; Diagnostic test: Hand-held video microscope; A handheld video microscope that looks at blood flow through the capillaries of the tongue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in tissue oxygenation	The difference in tissue oxygen saturation (StO2) during the vascular occlusion test in the Emergency Department between septic patients who need critical care treatment (CCT) compared to patients requiring ward care. This will be measured in % change per second..	Up to 4 hours (from baseline); 28 days (follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline of tissue oxygenation	The difference in tissue oxygen saturation (StO2) at baseline in the Emergency Department between septic patients who need critical care treatment (CCT) compared to patients requiring ward care. This will be measured in %.	Up to 4 hours (from baseline); 28 days (follow-up)
Difference in blood flow of the micro-circulation (microvascular flow index)	Differences in the flow of blood through small blood vessels underneath the tongue between the difference between septic patients who need critical care treatment (CCT) compared to patients requiring ward care. This will be measured by the Microvascular Flow Index (arbitrary units) which is a validated measurement assessing micro-circulatory flow.	Up to 4 hours (from baseline); 28 days (follow-up)
Difference in blood flow of the micro-circulation (perfused vessel density)	Differences in the flow of blood through small blood vessels underneath the tongue between the difference between septic patients who need critical care treatment (CCT) compared to patients requiring ward care. This will be measured by the perfused vessel density (measured in mm/mm2) which is a validated measurement assessing micro-circulatory flow.	Up to 4 hours (from baseline); 28 days (follow-up)
Difference in blood lactate levels	The difference in the blood tests of lactate between septic patients who need critical care treatment (CCT) compared to patients requiring ward care	Up to 4 hours (from baseline); 28 days (follow-up)
Difference in blood tests (MR-proADM)	The difference in the blood tests of MR-proADM between septic patients who need critical care treatment (CCT) compared to patients requiring ward care	Up to 4 hours (from baseline); 28 days (follow-up)
Difference in blood tests (Procalcitonin)	The difference in the blood tests of Procalcitonin (PCT) between septic patients who need critical care treatment (CCT) compared to patients requiring ward care	Up to 4 hours (from baseline); 28 days (follow-up)
Correlation of extra investigations with standard patient outcomes	Looking at whether tissue oxygenation, buccal microcirculation (blood flow under the tongue) and biomarkers and correlation with clinical outcomes such as organ failure (SOFA) scores, 28-day hospital mortality, and length of hospital and ICU stay.	Up to 4 hours (from baseline); 28 days (follow-up)

Collaborators and Investigators

• Sponsor: University Hospital Southampton NHS Foundation Trust
• Investigators: Study Director: Ahilanandan Dushianthan, PhD, University Hospital Southampton NHS Foundation Trust; Principal Investigator: James N Ward, BM, University Hospital Southampton NHS Foundation Trust

Publications and helpful links

General Publications

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• Jones S, Moulton C, Swift S, Molyneux P, Black S, Mason N, Oakley R, Mann C. Association between delays to patient admission from the emergency department and all-cause 30-day mortality. Emerg Med J. 2022 Mar;39(3):168-173. doi: 10.1136/emermed-2021-211572. Epub 2022 Jan 18.
• Linder A, Arnold R, Boyd JH, Zindovic M, Zindovic I, Lange A, Paulsson M, Nyberg P, Russell JA, Pritchard D, Christensson B, Akesson P. Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department. Crit Care Med. 2015 Nov;43(11):2378-86. doi: 10.1097/CCM.0000000000001265.
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Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2024
• Primary Completion (Estimated): August 6, 2025
• Study Completion (Estimated): August 6, 2025

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: February 7, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Estimated): December 2, 2024
• Last Update Submitted That Met QC Criteria: November 27, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: CRI0436

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie results in a publication will be shared
• IPD Sharing Time Frame: 6 months after publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No