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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
132
Daily subcutaneous administration of Interferon gamma during 5 days
Placebo during 5 days
CHU Limoges
Limoges, France
NOT_YET_RECRUITINGService civilo-militaire d'Anesthésie-Réanimation et Médecine Périopératoire
Lyon, France
RECRUITINGService de reanimation chirurgicale Hopital Croix-Rousse
Lyon, France
NOT_YET_RECRUITINGService de reanimation médicale hôpital de la Croix-Rousse
Lyon, France
RECRUITINGHôpital Edouard Herriot - Médecine intensive - réanimation
Lyon, France
NOT_YET_RECRUITINGService d'anesthésie-réanimation, unité de réanimation chirurgicale Picard
Nancy, France
NOT_YET_RECRUITINGMédecine intensive- Réanimation
Paris, France
NOT_YET_RECRUITINGService d'Anesthésie-réanimation-médecine intensive Hôpital Lyon Sud
Pierre-Bénite, France
RECRUITINGDépartement Anesthésie-Réanimation
Saint-Etienne, France
NOT_YET_RECRUITINGduration 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.
Time frame: Day 28
All-cause mortality in intensive care
Time frame: Day 28
Previous positive microbiological sample at inclusion becomes negative
Previous positive microbiological sample at inclusion becomes negative, i.e. pulmonary, urinary, blood cultures
Time frame: Day 5
Length of stay in intensive care unit
Time frame: Day 28
length of stay at hospital
Time frame: Day 28
occurrence of another episode of VAP before extubation
Time frame: Day 28
occurrence of another episode of infection acquired in intensive care unit
Time frame: Day 28
increase of monocytic HLA-DR expression above 8000 AB/C the day after the last dose of treatment (J5)
Time frame: Day 28
increase or decrease of blood leucocyte count at the day after the last dose of treatment (J5) in comparison to baseline
Time frame: Day 28
Evaluation of the economic efficiency of the administration of IFN-γ (assessed by the ACER (average cost-effectiveness ratio) method)
Evaluation of the cost-effectiveness of IFN-γ administration (assessed by the ACER (average cost-effectiveness ratio) method)
Time frame: Day 28
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