Clinical trial NCT02188992: Early PREdiction of Severe Sepsis I (ExPRES-Sepsis I) Study
Official title: Early Prediction of Severe Sepsis (ExPRESSepsis) Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Keywords: Sepsis
Immune activation
Systemic Inflammation
Emergency Medicine
Critical Care
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: Technology Strategy Board, United Kingdom
name: Becton, Dickinson and Company
First posted: 2014-07-14
Enrollment: 401
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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


Eligibility criteria: 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)

Primary outcomes:
measure: Development of septic shock
timeFrame: Within first 72 hours
measure: Confirmation of suspected infection
timeFrame: within first 72 hours
Secondary outcomes:
measure: Hospital outcome (lived/died)
timeFrame: Within first 72 hours
measure: Time to septic shock onset
timeFrame: Within the first 72 hours
measure: Death from sepsis
timeFrame: Within first 72 hours
measure: Organ dysfunction, total and individual organs as determined by SOFA score
timeFrame: within first 72 hours
measure: subsequent admission to critical care
timeFrame: within first 72 hours
measure: Changes in immune activation in those patients who develop any of the events mention in previous outcomes (i.e. septic shock, death, organ dysfunction, admission to critical care)
timeFrame: within first 72 hours
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: London
country: United Kingdom
facility: St Thomas' Hospital
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
Study officials:
affiliation: NHS Lothian/University of Edinburgh
name: Tim S Walsh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Newcastle-upon-Tyne Hospitals NHS Trust
name: John Wright, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Manu Shankar-Hari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cambridge
name: Andrew Conway Morris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Newcastle University
name: John Simpson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NHS Lothian/University of Edinburgh
name: Alasdair Gray, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.