Prevention of secondary infections by interferon-gamma in ICU-acquired sustained immune suppression in France: study protocol of the PLATINIUM randomised trial

Introduction Some intensive care unit (ICU) patients develop an extremely deep and sustained immunosuppression that increases the risk of secondary infections and can ultimately compromise survival. Thanks to an easily accessible and simplified immune monitoring to identify immunological failure, a personalised immune restoration approach is now feasible. Among the different therapeutic strategies in this field, interferon gamma (IFN-γ) is probably the most interesting drug to reduce the burden of secondary infections in the ICU. Methods and analysis This is a two parallel group multicentre blinded add-on randomised trial comparing immunorestoration by subcutaneous injection of IFN-γ to standard of care in targeted ICU patients. The study will be performed in 23 ICUs in France. Patients hospitalised in the ICU for a week, with multiple organ failure defined by a sequential organ failure assessment score ≥6 during this first week, will be enrolled. If within 96 hours after inclusion, these patients express immunosuppressed features defined by a low absolute lymphocyte count (<1000/×10⁹/L) and low expression of human leucocyte antigen-DR (HLA-DR) on monocytes (<8000antibodies bound per cell [Ab/c]) they will be randomised (1:1) to receive either five subcutaneous injections of IFN-γ or placebo in addition to standard of care. The primary outcome will be the incidence of secondary infection episodes at day 90 validated by an independent adjudication committee based on the current definitions (Centers for Disease Control and Prevention surveillance definitions). Secondary outcomes will be all-cause ICU mortality at day 90, length of stay in the ICU and in the hospital at day 90, antibiotic and antifungal consumption at day 90, percentage of biological immune restoration (defined as a monocytic HLA-DR >13 500 antibodies bound per cell and an absolute lymphocyte count >1200×10⁹/L) at day 10, healthcare costs at day 90 and rate of serious adverse reactions and suspected unexpected serious adverse reaction at day 90. We plan to randomise 326 patients. Ethics and dissemination The study will be implemented in accordance with European regulations and was independently reviewed and approved by the French Ethics Committee Comité de Protection des Personnes Ile de France III (EUCT number: 2024-516780-93-00). The results will be reported in international peer-reviewed journals and presented at international and national conferences.