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Peer-reviewedCC BY-NC 4.0BMJ Open

Effect of interferon gamma as a treatment for post-aggressive immunosuppression in critically ill (INFINITY trial): study protocol for a randomised Bayesian double-blind controlled trial

  • Charles de Roquetaillade1,2,3
  • Alexandre Joseph1,2,3
  • Antoine Kimmoun4
  • Francois Depret1,3
  • Jean-Michel Constantin3,5,6
  • Bruno Megarbane1,3
  • Bruno Francois7
  • Eric Vicaut1,3
  • Benjamin Chousterman1,2,3
7 affiliations
  1. 1Université Paris Cité, Paris, France
  2. 2Department of Anesthesiology and Critical Care, Hôpital Lariboisière, Paris, France
  3. 3Assistance Publique Hopitaux de Paris, Paris, France
  4. 4University Hospital Centre Nancy, Nancy, France
  5. 5Department of Anesthesiology and Critical Care, University Hospital Pitié Salpêtrière, Paris, France
  6. 6GRC 29, AP-HP, DMU DREAM, Sorbonne University, Paris, France
  7. 7University of Limoges, Limoges, France
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Abstract

Introduction: Critically ill patients frequently develop a delayed immune dysfunction after the initial insult, commonly referred to as post-aggressive immunosuppression (PAIS). Persistently reduced monocytic human leucocyte antigen-DR (mHLA-DR) expression is a widely used biomarker of PAIS and has been associated with intensive care unit (ICU)-acquired infections, prolonged organ support and excess late morbidity and mortality. To date, no immunostimulatory strategy has proven efficacy in improving patient-centred outcomes in this population. Interferon gamma-1b (IFN-γ1b) can restore monocyte function and antigen presentation in experimental and clinical settings and has shown biological plausibility and acceptable tolerability in critically ill patients. The INFINITY trial aims to determine whether short-course IFN-γ1b, initiated in patients with biomarker-defined PAIS, increases ventilator-free days compared with placebo.

Methods and analysis: INFINITY is a national, multicentre, phase II, Bayesian, superiority, randomised, placebo-controlled, double-blind, parallel-group trial with a 1:1 allocation ratio conducted in 6 ICUs in France. Adult ICU patients (≥18 years) with high initial severity (Sequential Organ Failure Assessment (SOFA) at ICU admission ≥6), receiving invasive mechanical ventilation at inclusion, and presenting with mHLA-DR <8000 AB/C measured between days 5 and 10 are eligible. Key non-inclusion criteria include pre-existing immunodeficiency, expected prolonged ventilation due to chronic conditions and contraindication to IFN-γ1b. Randomisation is centralised via a secure electronic system and stratified by centre. Participants receive either IFN-γ1b (Imukin) 2×106 IU (0.1 mg) subcutaneously every 24 hours for 3 consecutive days or matched placebo (0.9% sodium chloride), in addition to standard care. The primary endpoint is ventilator-free days alive at day 28. Secondary endpoints include mHLA-DR kinetics (day 0–7), lymphocyte count, ICU-acquired infections, antibiotic-free days, ICU-free days, SOFA kinetics and all-cause mortality at day 28 and day 90, alongside safety outcomes. A total of 170 participants (85 per group) are planned. Analyses will follow the intention-to-treat principle using Bayesian models with pre-specified interim analyses and stopping guidelines.

Ethics and dissemination: The study will be conducted in accordance with European regulations and was independently reviewed and approved by the French Ethics Committee Comité de Protection des Personnes Ile de France (EUCT number: 2023–5 06 725-11-00). The results will be reported in international peer-reviewed journals and presented at international and national conferences.

Trial registration number: ClinicalTrials.gov, NCT06694740; registered on 19 November 2024 (submitted 12 November 2024). Available at: https://clinicaltrials.gov/study/NCT06694740.

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Cite

BibTeXRIS
BibTeX
@article{roquetaillade2026effect,
  title = {{Effect of interferon gamma as a treatment for post-aggressive immunosuppression in critically ill (INFINITY trial): study protocol for a randomised Bayesian double-blind controlled trial}},
  author = {Charles de Roquetaillade and Alexandre Joseph and Antoine Kimmoun and Francois Depret and Jean-Michel Constantin and Bruno Megarbane and Bruno Francois and Eric Vicaut and Benjamin Chousterman},
  journal = {BMJ Open},
  year = {2026},
  month = oct,
  doi = {10.1136/bmjopen-2026-122953},
  url = {https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-122953},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Effect of interferon gamma as a treatment for post-aggressive immunosuppression in critically ill (INFINITY trial): study protocol for a randomised Bayesian double-blind controlled trial
AU  - Charles de Roquetaillade
AU  - Alexandre Joseph
AU  - Antoine Kimmoun
AU  - Francois Depret
AU  - Jean-Michel Constantin
AU  - Bruno Megarbane
AU  - Bruno Francois
AU  - Eric Vicaut
AU  - Benjamin Chousterman
PY  - 2026
DA  - 2026/10/26
JO  - BMJ Open
DO  - 10.1136/bmjopen-2026-122953
UR  - https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-122953
AB  - Introduction: Critically ill patients frequently develop a delayed immune dysfunction after the initial insult, commonly referred to as post-aggressive immunosuppression (PAIS). Persistently reduced monocytic human leucocyte antigen-DR (mHLA-DR) expression is a widely used biomarker of PAIS and has been associated with intensive care unit (ICU)-acquired infections, prolonged organ support and excess late morbidity and mortality. To date, no immunostimulatory strategy has proven efficacy in improving patient-centred outcomes in this population. Interferon gamma-1b (IFN-γ1b) can restore monocyte function and antigen presentation in experimental and clinical settings and has shown biological plausibility and acceptable tolerability in critically ill patients. The INFINITY trial aims to determine whether short-course IFN-γ1b, initiated in patients with biomarker-defined PAIS, increases ventilator-free days compared with placebo.  Methods and analysis: INFINITY is a national, multicentre, phase II, Bayesian, superiority, randomised, placebo-controlled, double-blind, parallel-group trial with a 1:1 allocation ratio conducted in 6 ICUs in France. Adult ICU patients (≥18 years) with high initial severity (Sequential Organ Failure Assessment (SOFA) at ICU admission ≥6), receiving invasive mechanical ventilation at inclusion, and presenting with mHLA-DR <8000 AB/C measured between days 5 and 10 are eligible. Key non-inclusion criteria include pre-existing immunodeficiency, expected prolonged ventilation due to chronic conditions and contraindication to IFN-γ1b. Randomisation is centralised via a secure electronic system and stratified by centre. Participants receive either IFN-γ1b (Imukin) 2×106 IU (0.1 mg) subcutaneously every 24 hours for 3 consecutive days or matched placebo (0.9% sodium chloride), in addition to standard care. The primary endpoint is ventilator-free days alive at day 28. Secondary endpoints include mHLA-DR kinetics (day 0–7), lymphocyte count, ICU-acquired infections, antibiotic-free days, ICU-free days, SOFA kinetics and all-cause mortality at day 28 and day 90, alongside safety outcomes. A total of 170 participants (85 per group) are planned. Analyses will follow the intention-to-treat principle using Bayesian models with pre-specified interim analyses and stopping guidelines.  Ethics and dissemination: The study will be conducted in accordance with European regulations and was independently reviewed and approved by the French Ethics Committee Comité de Protection des Personnes Ile de France (EUCT number: 2023–5 06 725-11-00). The results will be reported in international peer-reviewed journals and presented at international and national conferences.  Trial registration number: ClinicalTrials.gov, NCT06694740; registered on 19 November 2024 (submitted 12 November 2024). Available at: https://clinicaltrials.gov/study/NCT06694740.
SN  - 2044-6055
SN  - 2044-6055
ER  -