Human Recombinant Interferon Gamma in the Treatment of Ventilator-acquired Pneumonia in ICU Patients

NCT05843786 | Recruiting Phase 3 DMC

• 2 other identifiers: 69HCL22_08512022-502229-16-00
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 9

Brief Summary

Clinical presentation of patients after severe injury such as a severe infection, trauma or extensive burns is characterized by the simultaneous occurrence of dysregulation of the initial inflammatory response and immunosuppression associating quantitative and functional alterations of innate and adaptive immune cells. These acquired immune dysfunctions have been associated with an increased susceptibility to nosocomial infections, foremost among which are ventilator-associated pneumonia (VAP). Despite the implementation of a set of preventive measures, the incidence of these VAP remains high in intensive care, with rates in Europe of 1.5% per day of ventilation. Post-aggressive immunosuppression is characterized by the decrease in the expression of HLA-DR (belonging to the type II major histocompatibility complex, MHC-II) on the surface of monocytes (mHLA-DR). The administration of interferon gamma (IFNγ) can restore the level of mHLA-DR and may possibly improve the prognosis as an adjuvant therapy associated to antibiotics. However, the level of proof of this therapeutic strategy is low, limited to small cohorts of patients, or clinical studies without prior immunodepression assessment. The objective of this study is to conduct a randomized, double-blind, placebo-controlled superiority trial to assess the effect of IFNγ administration on the duration of mechanical ventilation following the first episode of VAP in patients having an HLA-DR \< 8000 AB/C All reported data about recombinant human IFNγ 1b for the control of secondary infections in patients with septic shock used the dose of 100 micrograms per day by subcutaneous route for 3 to 5 days . At this dose, no retrospective study has reported any serious adverse effects and recombinant human IFNγ 1b allows an increase in monocyte membrane expression of mHLA-DR.

Conditions

Pneumonia, Ventilator-Associated

Keywords

Critical Illness; Interferon-gamma; Immunodepression; Sepsis; Trauma; Monocyte HLA-DR; immunostimulation

Outcome Measures

Primary Outcomes (1)

• duration of mechanical ventilation assessed from the first day of VAP diagnosis

  mechanical ventilation-free days (VFD) from extubation through D28. A beneficial effect of using recombinant human interferon gamma-1b would be a statistically significant increase in VFD in patients receiving study drug in this setting compared to the group receiving placebo.

  Day 28

Secondary Outcomes (9)

• All-cause mortality in intensive care

  Day 28

• Previous positive microbiological sample at inclusion becomes negative

  Day 5

• Length of stay in intensive care unit

  Day 28

• length of stay at hospital

  Day 28

• occurrence of another episode of VAP before extubation

  Day 28

Study Arms (2)

Interferon gamma treatment

EXPERIMENTAL

Interferon gamma treatment (100 micrograms /day during 5 days)

Drug: Interferon gamma

Placebo

PLACEBO COMPARATOR

The comparator drug (placebo) is an injectable solution of sodium chloride 0.9%

Drug: Placebo

Interventions

Interferon gamma DRUG

Daily subcutaneous administration of Interferon gamma during 5 days

Interferon gamma treatment

Placebo DRUG

Placebo during 5 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult patients hospitalized in intensive care unit
• under mechanical ventilation for more than 5 days
• having a first episode of VAP (with a Clinical Pulmonary Infectious Score (CPIS score) \>6)
• treated with antibiotics for less than 24 hours
• with monocyte HLA-DR \< 8000 AB/C
• written informed consent signed by the patient's trusted support person, or in the absence of the patient's representative and taking into account the agreement of the relative obtained by telephone emergency certificate completed and signed by the investigator
• membership of a social security scheme

You may not qualify if:

• inability to administer the first dose of treatment in the study within 48 hours of the start of antibiotic therapy (antibiotic therapy for VAP)
• Noradrenaline \> 0.25 mcg/kg/min
• Immunosuppression, defined by:
• solid tumor with chemotherapy in the last 3 months
• progressive metastatic disease
• hematological disease
• solid organ transplantation
• HIV infection (AIDS stage or not)
• corticosteroid therapy at any dose for more than 3 months
• ≥ 1 mg/kg of Prednisone equivalent for more than 7 days
• immunosuppressive therapy
• Head and/or cervical spine trauma : with a predictable impact on the duration of mechanical ventilation (left to the investigator's judgement), the investigator will assess whether the patient meets the following neurological criteria for extubation during their recovery:
• A level of consciousness assessed as 0 or 1 on the Richmond Agitation-Sedation Scale (RASS)
• FiO2 \<40%
• PEEP level \<5 cmH2O

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (9)

CHU Limoges

Limoges, France

NOT YET RECRUITING

Service civilo-militaire d'Anesthésie-Réanimation et Médecine Périopératoire

Lyon, 69003, France

RECRUITING

Service de reanimation chirurgicale Hopital Croix-Rousse

Lyon, 69004, France

NOT YET RECRUITING

Service de reanimation médicale hôpital de la Croix-Rousse

Lyon, 69004, France

RECRUITING

Hôpital Edouard Herriot - Médecine intensive - réanimation

Lyon, France

NOT YET RECRUITING

Service d'anesthésie-réanimation, unité de réanimation chirurgicale Picard

Nancy, 54511, France

NOT YET RECRUITING

Médecine intensive- Réanimation

Paris, 75014, France

NOT YET RECRUITING

Service d'Anesthésie-réanimation-médecine intensive Hôpital Lyon Sud

Pierre-Bénite, 69395, France

RECRUITING

Département Anesthésie-Réanimation

Saint-Etienne, 42055, France

NOT YET RECRUITING

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Critical Illness; Sepsis; Wounds and Injuries

Interventions

Interferon-gamma

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Macrophage-Activating Factors; Lymphokines; Proteins; Biological Factors

Study Officials

• Anne-Claire LUKASZEWICZ, Pr

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne-Claire LUKASZEWICZ, Pr

CONTACT

472 11 13 27; anne-claire.lukaszewicz@chu-lyon.fr

Camille BOUCHENY

CONTACT

4 26 73 27 39; Camille.boucheny@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: May 6, 2023
• Study Start: June 30, 2023
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027
• Last Updated: November 21, 2025

Record last verified: 2025-11

Locations

FR (9)