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

NCT ID: NCT02188992

Last Updated: 2016-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

401 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-01-31

Study Completion Date

2016-01-31

Brief Summary

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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

Detailed Description

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Conditions

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Sepsis

Keywords

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Sepsis Immune activation Systemic Inflammation Emergency Medicine Critical Care

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort 1

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

No interventions assigned to this group

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).

No interventions assigned to this group

Cohort 3

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

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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)
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Technology Strategy Board, United Kingdom

OTHER

Sponsor Role collaborator

Becton, Dickinson and Company

INDUSTRY

Sponsor Role collaborator

University of Edinburgh

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tim S Walsh, MD

Role: PRINCIPAL_INVESTIGATOR

NHS Lothian/University of Edinburgh

John Wright, MD

Role: PRINCIPAL_INVESTIGATOR

Newcastle-upon-Tyne Hospitals NHS Trust

Manu Shankar-Hari, MD

Role: PRINCIPAL_INVESTIGATOR

Guy's and St Thomas' NHS Foundation Trust

Andrew Conway Morris, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cambridge

John Simpson, MD

Role: PRINCIPAL_INVESTIGATOR

Newcastle University

Alasdair Gray, MD

Role: PRINCIPAL_INVESTIGATOR

NHS Lothian/University of Edinburgh

Locations

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Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Site Status

St Thomas' Hospital

London, , United Kingdom

Site Status

Royal Victoria Infirmary

Newcastle, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 30291379 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27481622 (View on PubMed)

Other Identifiers

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2013/0267

Identifier Type: -

Identifier Source: org_study_id