Critically ill patients in intensive care units who are at particularly high risk of secondary (hospital-acquired) infection Infections and Infestations
Conditions
Interventions
After informed consent has been received and eligibility confirmed, patients will be randomised into the trial. Randomisation will be performed using the Sealed Envelope system, a secure, 24-hour web-
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patient has been managed in ICU for =2 days 2. Either (a) intubated and receiving mechanical ventilation or/and (b) on both vasopressors (to control blood pressure) and renal replacement therapy 3. Age =18 years old 4. Informed, written consent obtained from a personal legal representative or professional legal representative 5. Blood monocyte HLA-DR level of <8000 anti-monocyte HLA-DR antibodies per cell 6. Negative pregnancy test in women of childbearing potential
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 29/07/2025: 1. Breastfeeding or pregnancy 2. Any admission with status epilepticus or current diagnosis of epilepsy that requires treatment with anti-epileptic medications 3. Chronic liver disease with Child-Pugh score C or worse 4. Known allergy to interferons or latex 5. Concomitant enrolment in another interventional trial, except where a co-enrolment agreement exists 6. Solid organ or bone marrow transplantation 7. Patient is under active haematological malignancy surveillance 8. Current active systemic chemotherapy or immunotherapy for cancer (hormonal treatment will not exclude patients) known human immunodeficiency virus (HIV) with a documented CD4 count of 4 times the upper limit of normal according to the recruiting hospital’s clinical reference range 11. Known 2nd or 3rd degree heart block 12. History of severe heart failure or history of New York Heart Association (NYHA) heart failure score of 3 or 4 13. Proposed use of vaccines in the 10 days from randomisation 14. Known receipt of a vaccination in the 28 days prior to admission to the ICU 15. Consultant in charge of the patient’s care considers the patient’s participation inappropriate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Antibiotic-free days over a 14-day period (AFD-14). AFD-14 is defined as the number of 24-hour periods in which participants were alive and in which intravenous/enteral antibiotics were not used to treat active infection. AFD-14 is measured from days 3-16 inclusive. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Infection-free survival (IFS). IFS is a composite measure that takes into account the development of new infection or death. The unit of infection-free survival is a day. If a participant is alive and has not developed a new infection for a given day, this counts as one day of infection-free survival. IFS is counted from randomisation (i.e. day 0) to day 16 inclusive. 2. Antibiotic days. The number of days on which an antibiotic, including antimicrobial agents and anti-fungal agents used intravenously or enterally to treat active infection, was taken from days 3-16 inclusive. 3. New infections. A new infection is defined as a new episode of sepsis, pneumonia, abdominal infection, blood-stream infection, catheter/line-associated infection, urinary tract infection, central nervous system infection, surgical site infection, cellulitis, new Clostridium difficile infection, or any other acute infection. New infections from days 0-16 will be recorded. 4. New antibiotic prescriptions. The number of new antibiotic prescriptions started on days 3-16 inclusive will be recorded. 5. Sequential Organ Failure Assessment (SOFA) score. The SOFA score will be recorded on the day of randomisation (counted as day 0) and on the days on which the 2nd and 3rd doses of IFNg/placebo are given, if the participant is still in the ICU. 6. Change in mHLA-DR. For each participant the difference in mAb/cell will be calculated for the intervals between the 1st and 2nd mHLA-DR results; the 1st and 3rd mHLA-DR results; and the 2nd and 3rd mHLA-DR results. 7. Time on intubation and mechanical ventilation, defined as days intubated and mechanically ventilated from randomisation to day 30 post-randomisation. 8. Length of ICU stay, defined as the time from admission to ICU to discharge from the ICU, and measured up to day 30 from randomisation. 9. Safety of IFNg assessed by comparing the frequency of SARs in the arms 10. Potential toxicity: routinely collected data will be reviewed to assess p | — |
Countries
England, Northern Ireland, United Kingdom
Contacts
Public ContactJaki Hodgson
Outcome results
None listed