Clinical trial NCT02186522: Immune Failure in Critical Therapy (INFECT) Study
Official title: Immune Failure in Critical Therapy(INFECT) Study: Phenotyping Immune Cell Dysfunction to Predict Outcomes in Critically Ill Adults
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sepsis
Septic Shock
Keywords: Sepsis
Septic shock
Critical care
Immune dysfunction
Inflammatory markers
Neutrophil
Monocyte
Tregs
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: Technology Strategy Board, United Kingdom
name: Becton, Dickinson and Company
First posted: 2014-07-10
Enrollment: 168
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: Critical Care patients who are expected to remain in ICU for at least 48 hours, and require the external support of one or more organs (invasive ventilation, inotropes/vasopressors or renal replacement therapy) and who are not expected to die within 48 hours of study entry.

Brief summary: Patients admitted to intensive care units (ICU) are at high risk of developing secondary infections, and this is in part due to dysfunction or failure of their 'germ killing' functions (the immune system). Our group has recently identified three signatures of immune system failure which can be readily detected on a blood sample, and importantly, appear to predict the chances of developing secondary infection. Such a test would have major benefits for the management of patients in intensive care if it can be translated into a test usable in everyday clinical practice. This study aims to validate our original findings in a cohort of patients from multiple ICUs, using a test which will be suitable for everyday clinical practice, and thus take the next step towards developing a market-ready test.

Study hypothesis:

Measurement of neutrophil CD88, monocyte HLA-DR and percentage Tregs will accurately predict the risk of nosocomial infection.


Eligibility criteria: Inclusion Criteria:

* Age \>16 (\>18 in England)
* Requiring level 3 care (i.e. requiring invasive support of respiratory system alone, or two or more other organ systems (haemofiltration, inotropes/vasopressors)
* Predicted to remain in ICU for at least 48 hours,

Exclusion Criteria:

* Not expected to survive for a further 24 hours
* Known or suspected ICU-acquired infection at time of screening (non-ICU acquired nosocomial infection - i.e. non-ICU healthcare associated infection is NOT and exclusion)
* Known inborn errors of immune function
* Immunosuppression (corticosteroids up to 400mg hydrocortisone equivalent daily dose permitted)
* HIV infection
* Pregnancy
* Previously enrolled in the study

Primary outcomes:
measure: The development of immune dysfunction (see below) and its association with ICU-acquired infection within the 16 day study period.
timeFrame: Within the first 16 days
Secondary outcomes:
measure: ICU Outcome (lived/died)
timeFrame: Within first 16 days
measure: Death from sepsis
timeFrame: Within first 16 days
measure: Organ dysfunction as determined by SOFA score
timeFrame: Within first 14 days
measure: Length of ICU stay
timeFrame: Up to 3 months (for current hospital admission only)
measure: Duration of organ support in ICU
timeFrame: Within first 14 days
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: London
country: United Kingdom
facility: St Thomas' Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
Study officials:
affiliation: University of Cambridge
name: Andrew Conway Morris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NHS Lothian/University of Edinburgh
name: Tim S Walsh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Newcastle University
name: John Simpson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: City Hospitals Sunderland NHS Foundation Trust
name: Alistair Roy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Alun Brown
role: PRINCIPAL_INVESTIGATOR
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Manu Shankar-Hari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NHS Lothian (Western General Hospital)
name: Anthony Bateman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Conway Morris A, Datta D, Shankar-Hari M, Stephen J, Weir CJ, Rennie J, Antonelli J, Bateman A, Warner N, Judge K, Keenan J, Wang A, Burpee T, Brown KA, Lewis SM, Mare T, Roy AI, Hulme G, Dimmick I, Rossi AG, Simpson AJ, Walsh TS. Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study. Intensive Care Med. 2018 May;44(5):627-635. doi: 10.1007/s00134-018-5247-0. Epub 2018 Jun 7.
citation: Conway Morris A, Datta D, Shankar-Hari M, Weir CJ, Rennie J, Antonelli J, Rossi AG, Warner N, Keenan J, Wang A, Brown KA, Lewis S, Mare T, Simpson AJ, Hulme G, Dimmick I, Walsh TS. Predictive value of cell-surface markers in infections in critically ill patients: protocol for an observational study (ImmuNe FailurE in Critical Therapy (INFECT) Study). BMJ Open. 2016 Jul 18;6(7):e011326. doi: 10.1136/bmjopen-2016-011326.