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

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05843786

Collaborator

(none)

132

Enrollment

Locations

Arms

Anticipated Duration (Months)

18.9

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Ventilator-Associated	Drug: Interferon gamma Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

132 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Interferon gamma treatment Interferon gamma treatment (100 micrograms /day during 5 days)	Drug: Interferon gamma Daily subcutaneous administration of Interferon gamma during 5 days
Placebo Comparator: Placebo The comparator drug (placebo) is an injectable solution of sodium chloride 0.9%	Drug: Placebo Placebo during 5 days

Arm

Intervention/Treatment

Experimental: Interferon gamma treatment

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

Drug: Interferon gamma

Daily subcutaneous administration of Interferon gamma during 5 days

Placebo Comparator: Placebo

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

Drug: Placebo

Placebo during 5 days

Outcome Measures

Primary Outcome Measures

duration of mechanical ventilation assessed from the first day of VAP diagnosis [Day 28]
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.

Secondary Outcome Measures

All-cause mortality in intensive care [Day 28]
Previous positive microbiological sample at inclusion becomes negative [Day 5]
Previous positive microbiological sample at inclusion becomes negative, i.e. pulmonary, urinary, blood cultures
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]
occurrence of another episode of infection acquired in intensive care unit [Day 28]
increase of monocytic HLA-DR expression above 8000 AB/C the day after the last dose of treatment (J5) [Day 28]
increase or decrease of blood leucocyte count at the day after the last dose of treatment (J5) in comparison to baseline [Day 28]
Evaluation of the economic efficiency of the administration of IFN-γ (assessed by the ACER (average cost-effectiveness ratio) method) [Day 28]
Evaluation of the cost-effectiveness of IFN-γ administration (assessed by the ACER (average cost-effectiveness ratio) method)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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)

treated with antibiotics for less than 24 hours
with monocyte HLA-DR < 8000 AB/C

Exclusion Criteria:

VAP requiring the introduction of pressor amines
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 spinal trauma
Cardiocirculatory arrest
Burn patient
Cirrhosis with Child B or C score
Infection with Aspergillus spp.
Refusal to participate
Patient participating in another interventional research in progress or including an exclusion period still in progress at pre-inclusion (excluding interventional research of 2° not interfering with the endpoints of the study according to the judgment of the principal investigator)
Lack of social coverage
Patient under curatorship or guardianship
Pregnant or breastfeeding women
Patient admitted to intensive care for SARS-Cov2 pneumonia
Known allergy to latex
Hypersensitivity to the active substance (interferon gamma-1b) or known hypersensitivity to related products, such as another interferon, or to any of the following excipients: Mannitol, Disodium succinate hexahydrate, Succinic acid, polysorbate 20
Existence of chronic heart disease with FeVG<45%
Major hepatic impairment (total bilirubin>60 mg/L or 102 mcmol/L, equivalent to 3 SOFA points)
thrombocytopenia <50000/mm3 (equivalent to 3 SOFA points) AST and/or ALT > 5N Lipase > 3N Severe chronic renal failure (creatinine clearance MDRD< 10 ml/min/1.73m2)
Thrombocytopenia <50,000/mm3 (equivalent to 3 SOFA points)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Service civilo-militaire d'Anesthésie-Réanimation et Médecine Périopératoire	Lyon	France	69003
2	Service de reanimation chirurgicale Hopital Croix-Rousse	Lyon	France	69004
3	Service de reanimation médicale hôpital de la Croix-Rousse	Lyon	France	69004
4	Service d'anesthésie-réanimation, unité de réanimation chirurgicale Picard	Nancy	France	54511
5	Médecine intensive- Réanimation	Paris	France	75014
6	Service d'Anesthésie-réanimation-médecine intensive Hôpital Lyon Sud	Pierre-Bénite	France	69395
7	Département Anesthésie-Réanimation	Saint-Étienne	France	42055