Can interferon gamma prevent infection in critically ill patients at highest risk? A phase II randomised controlled trial - INFINIT (INterFeron to reduce INfection in InTensive care units)
Critically ill patients in intensive care units who are at particularly high risk of secondary (hospital-acquired) infection
Current interventions as of 10/08/2026: 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-based randomisation system. The intervention is three subcutaneous injections over a week of either interferon gamma (IFNg) at 100 mcg vs placebo 0.5 ml. These preparations will be administered in a syringe on the basis of the randomisation allocation. The first administration of IMP will be considered day 0. The second dose will be given at least 48 hours later. The third dose will be given at least 48 hours after the second dose. The IMP is to be administered three times over 7 days. Previous 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-based randomisation system. The intervention is three subcutaneous injections over a week (three times in a week) of either interferon-gamma (IFNg) or sterile water for injection (WFI) as a placebo. Prior to the interim analysis, there are four treatment groups, interferon-gamma treatment at three different doses and a placebo treatment. After an interim analysis, the best interferon-gamma treatment dose will be chosen and patients will be recruited into one of two groups, the best interferon-gamma treatment dose and placebo. The four treatment groups are: 1. IFNg 100 mcg 2. IFNg 50 mcg 3. IFNg/placebo where the first dose is 100 mcg IFNg sc, the second dose is 100 mcg sc if the mHLA-DR is <8000 mAb/cell (if it is ≥8000 mAb/cell placebo is given sc), and the third dose is 100 mcg sc if the mHLA-DR is <8000 mAb/cell (if it is ≥8000 mAb/cell placebo is given sc) 4. Placebo (sterile WFI) The preparations will be administered in a syringe on the basis of the randomisation allocation. The first administration is expected t
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 Added 10/08/2026: 7. Is an inpatient in an intensive care unit environment
Current exclusion criteria as of 10/08/2026: 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 <300 cells per cubic millilitre in the last 6 months in those not on renal replacement therapy, an estimated glomerular filtration rate <15 ml/min/1.73 metres squared 9. Blood neutrophil count < 0.5x10^9/L 10. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥8 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 live vaccines in the 10 days from randomisation until 10 days after the last dose of IFNg/placebo 14. Known receipt of a live vaccination in the 28 days prior to screening (based on information available at the time of screening as part of routine clinical care 15. Consultant in charge of the patient’s care considers the patient’s participation inappropriate Previous 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