Immune Failure in Critical Therapy (INFECT) Study (INFECT)

Immune Failure in Critical Therapy(INFECT) Study: Phenotyping Immune Cell Dysfunction to Predict Outcomes in Critically Ill Adults

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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock

• Study Type: Observational
• Enrollment (Actual): 168

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh
  • London, United Kingdom, SE1 7EH
    • St Thomas' Hospital
  • Sunderland, United Kingdom, SR4 7TP
    • Sunderland Royal Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Critical Care Patients; Patients staying in the ICU for at least 48 hours, requiring 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The development of immune dysfunction (see below) and its association with ICU-acquired infection within the 16 day study period.	Within the first 16 days

Secondary Outcome Measures

Outcome Measure	Time Frame
ICU Outcome (lived/died)	Within first 16 days
Death from sepsis	Within first 16 days
Organ dysfunction as determined by SOFA score	Within first 14 days
Length of ICU stay	Up to 3 months (for current hospital admission only)
Duration of organ support in ICU	Within first 14 days

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: Becton, Dickinson and Company; Technology Strategy Board, United Kingdom
• Investigators: Principal Investigator: Andrew Conway Morris, MD, University of Cambridge; Principal Investigator: Tim S Walsh, MD, NHS Lothian/University of Edinburgh; Principal Investigator: John Simpson, MD, Newcastle University; Principal Investigator: Alistair Roy, MD, City Hospitals Sunderland NHS Foundation Trust; Principal Investigator: Alun Brown, Guy's and St Thomas' NHS Foundation Trust; Principal Investigator: Manu Shankar-Hari, MD, Guy's and St Thomas' NHS Foundation Trust; Principal Investigator: Anthony Bateman, MD, NHS Lothian (Western General Hospital)

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: July 7, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimate): July 10, 2014

Study Record Updates

• Last Update Posted (Estimate): October 26, 2016
• Last Update Submitted That Met QC Criteria: October 25, 2016
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Septic shock; Critical care; Inflammatory markers; Sepsis; Tregs; Monocyte; Neutrophil; Immune dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Shock, Septic
• Other Study ID Numbers: 2014/0208