SepsisExPRESNCT02188992
Early PREdiction of Severe Sepsis I (ExPRES-Sepsis I) Study
An observational study of Sepsis, run by University of Edinburgh at 3 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Sepsis
- How many people
- 401 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Jan 2014to Jan 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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)
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA
St Thomas' Hospital
London, SE1 7EH
Royal Victoria Infirmary
Newcastle, NE1 4LP
About this study
Official title: Early Prediction of Severe Sepsis (ExPRESSepsis) Study
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.
Read more
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
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of septic shock
Measured: Within first 72 hours
Confirmation of suspected infection
Measured: within first 72 hours
Secondary outcomes (6)
Hospital outcome (lived/died)
Measured: Within first 72 hours
Time to septic shock onset
Measured: Within the first 72 hours
Death from sepsis
Measured: Within first 72 hours
Organ dysfunction, total and individual organs as determined by SOFA score
Measured: within first 72 hours
subsequent admission to critical care
Measured: within first 72 hours
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)
Measured: within first 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2014 (estimated)
- Study startJan 2014
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 401 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Technology Strategy Board, United Kingdom, Becton, Dickinson and Company
- Responsible party
- Sponsor
- Investigators
- Tim S Walsh, MD, Principal investigator, NHS Lothian/University of EdinburghJohn Wright, MD, Principal investigator, Newcastle-upon-Tyne Hospitals NHS TrustManu Shankar-Hari, MD, Principal investigator, Guy's and St Thomas' NHS Foundation TrustAndrew Conway Morris, MD, Principal investigator, University of CambridgeJohn Simpson, MD, Principal investigator, Newcastle UniversityAlasdair Gray, MD, Principal investigator, NHS Lothian/University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02188992
- Sponsor's protocol ID
- 2013/0267
- Acronym
- ExPRES
- Status last verified
- Jul 2014
- First submitted
- 7 Jul 2014
- Last updated
- 26 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30291379Datta 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.
PubMed 27481622
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Prediction of Severe Sepsis (ExPRESSepsis) Study
- ClinicalTrials.gov ID
- NCT02188992
- Acronym / sponsor ID
- ExPRES / 2013/0267
- Conditions
- Sepsis
- Keywords
- Sepsis, Immune activation, Systemic Inflammation, Emergency Medicine, Critical Care
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 401 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- Technology Strategy Board, United Kingdom, Becton, Dickinson and Company
- Study start
- Jan 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 14 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Development of septic shock
Time frame: Within first 72 hours
Confirmation of suspected infection
Time frame: within first 72 hours
6 secondary outcomes
Hospital outcome (lived/died)
Time frame: Within first 72 hours
Time to septic shock onset
Time frame: Within the first 72 hours
Death from sepsis
Time frame: Within first 72 hours
Organ dysfunction, total and individual organs as determined by SOFA score
Time frame: within first 72 hours
subsequent admission to critical care
Time frame: within first 72 hours
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)
Time frame: within first 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2016.
- Derived from this study: PubMed 30291379Shankar-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.
- Derived from this study: PubMed 27481622Datta 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim S Walsh, MD principal investigator
NHS Lothian/University of Edinburgh
John Wright, MD principal investigator
Newcastle-upon-Tyne Hospitals NHS Trust
Manu Shankar-Hari, MD principal investigator
Guy's and St Thomas' NHS Foundation Trust
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis, run by University of Edinburgh at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of septic shock (time frame: Within first 72 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02188992, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2016.