Early PREdiction of Severe Sepsis I (ExPRES-Sepsis I) Study

NCT02188992 | Completed

• 1 other identifier: 2013/0267
• Study Type: observational
• Target: 401
• Locations: 1 country
• Sites: 3

Brief Summary

Between 6 and 16% of patients presenting to hospital emergency departments have infections, with half of these having signs of systemic inflammation (known as 'sepsis'). A second issue is that, at time of presentation, it can be difficult to determine who has inflammation as a result of infection and who does not. Some of the patients with infections will deteriorate to organ failure ('severe sepsis') including failure of the heart and blood vessels to maintain normal blood pressure ('septic shock'). Septic shock as arguably the most dangerous form of severe sepsis is associated with a significant mortality, which can be reduced by early intervention. However identifying those patients who are at high risk of deteriorating to septic shock can be difficult on initial presentation to hospital, and thus these patients risk being 'triaged' to an inappropriate level of care and/or missing the crucial early interventions which can modify mortality. Equally failure to identify which patients have underlying infections can lead to potential inappropriate targeting of antibiotics. Existing clinical and laboratory tests are often unable to accurately identify those patients with infection, and those who are likely to deteriorate to severe sepsis and septic shock. Investigators in this group have recently identified several signatures of immune system activation which predict those patients who are likely to deteriorate, and which patients with suspected infection subsequently have this confirmed. Such tests would have major benefits for the management of patients with early suspected infection and sepsis if they can be translated into a test usable in everyday clinical practice. This study aims to determine the prevalence of these markers in a cohort of patients admitted with suspected sepsis, and their predictive ability for developing established septic shock. From this investigators aim to derive an optimal test, to be tested in a validation cohort (ExPRES-Sepsis II) which will be suitable for everyday clinical practice, and thus take the next step towards developing a market-ready test. Study hypothesis is: Measurement of markers of immune activation will allow i) Risk stratification for deterioration into severe sepsis ii) Risk stratification for death amongst patients presenting with sepsis iii) Identification of patients with confirmed sepsis

Conditions

Sepsis

Keywords

Sepsis; Immune activation; Systemic Inflammation; Emergency Medicine; Critical Care

Outcome Measures

Primary Outcomes (2)

• Development of septic shock

  Within first 72 hours

• Confirmation of suspected infection

  within first 72 hours

Secondary Outcomes (6)

• Hospital outcome (lived/died)

  Within first 72 hours

• Time to septic shock onset

  Within the first 72 hours

• Death from sepsis

  Within first 72 hours

• Organ dysfunction, total and individual organs as determined by SOFA score

  within first 72 hours

• subsequent admission to critical care

  within first 72 hours

Study Arms (3)

Cohort 1

Patients with sepsis syndrome, without criteria for severe sepsis/septic shock. These patients are recruited from the emergency department.

Cohort 2

Patients with community acquired sepsis syndrome REQUIRING critical care admission due to severity of sepsis. These patients are recruited from the critical care areas (ICU/HDU).

Cohort 3

Patients without sepsis syndrome. Age and gender matched to cohort 1, and recruited from Emergency Department.

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients in the initial 12 hours following presentation to hospital with suspected sepsis, i.e. patients with signs of systemic inflammation (i.e. meeting criteria for SIRS) where the treating clinician takes microbial samples and/or starts empiric antibiotics.

You may qualify if:

• Age \>16 (\>18 in England)
• SIRS criteria met (2 or more of White Cell Count (WCC) \>11 or \<4, Heart Rate (HR) \>90, Respiratory Rate (RR) \>20 or temp \>38 or \<36oC)
• Clinical suspicion of sepsis (cultures taken or antibiotics started)
• Enrolled within 12 hours of hospital admission

You may not qualify if:

• Acute pancreatitis
• Septic shock at time of enrolment
• Severe organ failure at time of enrolment (immediate requirement for ventilation, vasopressor or renal replacement therapy)
• Haematological malignancy
• Recent chemotherapy (past 2 weeks)
• Myelodysplastic syndromes
• Known neutropaenia
• HIV infection
• Pregnancy
• Blood transfusion \>4 units in past week
• Oral Corticosteroids for \>24 hours prior to enrolment
• Decision not for active therapy/ palliative care at admission
• Lacking in capacity to consent and nearest relative/welfare guardian not available for consultation and proxy consent (Scotland only)

Sponsors & Collaborators

• University of Edinburgh: lead
• Technology Strategy Board, United Kingdom: collaborator
• Becton, Dickinson and Company: collaborator

Study Sites (3)

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

St Thomas' Hospital

London, SE1 7EH, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, NE1 4LP, United Kingdom

Location

Related Publications (2)

• Shankar-Hari M, Datta D, Wilson J, Assi V, Stephen J, Weir CJ, Rennie J, Antonelli J, Bateman A, Felton JM, Warner N, Judge K, Keenan J, Wang A, Burpee T, Brown AK, Lewis SM, Mare T, Roy AI, Wright J, Hulme G, Dimmick I, Gray A, Rossi AG, Simpson AJ, Conway Morris A, Walsh TS. Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study. Intensive Care Med. 2018 Nov;44(11):1836-1848. doi: 10.1007/s00134-018-5389-0. Epub 2018 Oct 5.

  PMID: 30291379 DERIVED

• Datta D, Conway Morris A, Antonelli J, Warner N, Brown KA, Wright J, Simpson AJ, Rennie J, Hulme G, Lewis SM, Mare TA, Cookson S, Weir CJ, Dimmick I, Keenan J, Rossi AG, Shankar-Hari M, Walsh TS; ExPRES Sepsis Investigators. Early PREdiction of Severe Sepsis (ExPRES-Sepsis) study: protocol for an observational derivation study to discover potential leucocyte cell surface biomarkers. BMJ Open. 2016 Aug 1;6(8):e011335. doi: 10.1136/bmjopen-2016-011335.

  PMID: 27481622 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Samples of serum and plasma will be stored frozen.

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tim S Walsh, MD

  NHS Lothian/University of Edinburgh

  PRINCIPAL INVESTIGATOR

• John Wright, MD

  Newcastle-upon-Tyne Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

• Manu Shankar-Hari, MD

  Guy's and St Thomas' NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Andrew Conway Morris, MD

  University of Cambridge

  PRINCIPAL INVESTIGATOR

• John Simpson, MD

  Newcastle University

  PRINCIPAL INVESTIGATOR

• Alasdair Gray, MD

  NHS Lothian/University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2014
• First Posted: July 14, 2014
• Study Start: January 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: October 26, 2016

Record last verified: 2014-07

Locations

GB (3)