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

Primary Purpose

Pneumonia, Ventilator-Associated

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Interferon gamma
Placebo
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pneumonia, Ventilator-Associated focused on measuring Critical Illness, Interferon-gamma, Immunodepression, Sepsis, Trauma, Monocyte HLA-DR, immunostimulation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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) >6) treated with antibiotics for less than 24 hours with monocyte HLA-DR < 8000 AB/C Exclusion Criteria: 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 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)

Sites / Locations

  • Service civilo-militaire d'Anesthésie-Réanimation et Médecine PériopératoireRecruiting
  • Service de reanimation chirurgicale Hopital Croix-Rousse
  • Service de reanimation médicale hôpital de la Croix-Rousse
  • Service d'anesthésie-réanimation, unité de réanimation chirurgicale Picard
  • Médecine intensive- Réanimation
  • Service d'Anesthésie-réanimation-médecine intensive Hôpital Lyon Sud
  • Département Anesthésie-Réanimation

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Interferon gamma treatment

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

All-cause mortality in intensive care
Previous positive microbiological sample at inclusion becomes negative
Previous positive microbiological sample at inclusion becomes negative, i.e. pulmonary, urinary, blood cultures
Length of stay in intensive care unit
length of stay at hospital
occurrence of another episode of VAP before extubation
occurrence of another episode of infection acquired in intensive care unit
increase of monocytic HLA-DR expression above 8000 AB/C the day after the last dose of treatment (J5)
increase or decrease of blood leucocyte count at the day after the last dose of treatment (J5) in comparison to baseline
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)

Full Information

First Posted
April 12, 2023
Last Updated
September 13, 2023
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT05843786
Brief Title
Human Recombinant Interferon Gamma in the Treatment of Ventilator-acquired Pneumonia in ICU Patients
Acronym
IGNORANT
Official Title
Human Recombinant Interferon Gamma in the Treatment of Ventilator-acquired Pneumonia in ICU Patients
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 30, 2023 (Actual)
Primary Completion Date
July 30, 2025 (Anticipated)
Study Completion Date
July 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia, Ventilator-Associated
Keywords
Critical Illness, Interferon-gamma, Immunodepression, Sepsis, Trauma, Monocyte HLA-DR, immunostimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
132 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Interferon gamma treatment
Arm Type
Experimental
Arm Description
Interferon gamma treatment (100 micrograms /day during 5 days)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The comparator drug (placebo) is an injectable solution of sodium chloride 0.9%
Intervention Type
Drug
Intervention Name(s)
Interferon gamma
Intervention Description
Daily subcutaneous administration of Interferon gamma during 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo during 5 days
Primary Outcome Measure Information:
Title
duration of mechanical ventilation assessed from the first day of VAP diagnosis
Description
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
Secondary Outcome Measure Information:
Title
All-cause mortality in intensive care
Time Frame
Day 28
Title
Previous positive microbiological sample at inclusion becomes negative
Description
Previous positive microbiological sample at inclusion becomes negative, i.e. pulmonary, urinary, blood cultures
Time Frame
Day 5
Title
Length of stay in intensive care unit
Time Frame
Day 28
Title
length of stay at hospital
Time Frame
Day 28
Title
occurrence of another episode of VAP before extubation
Time Frame
Day 28
Title
occurrence of another episode of infection acquired in intensive care unit
Time Frame
Day 28
Title
increase of monocytic HLA-DR expression above 8000 AB/C the day after the last dose of treatment (J5)
Time Frame
Day 28
Title
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
Title
Evaluation of the economic efficiency of the administration of IFN-γ (assessed by the ACER (average cost-effectiveness ratio) method)
Description
Evaluation of the cost-effectiveness of IFN-γ administration (assessed by the ACER (average cost-effectiveness ratio) method)
Time Frame
Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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) >6) treated with antibiotics for less than 24 hours with monocyte HLA-DR < 8000 AB/C Exclusion Criteria: 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 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anne-Claire LUKASZEWICZ, Pr
Phone
472 11 13 27
Ext
+33
Email
anne-claire.lukaszewicz@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Camille BOUCHENY
Phone
4 26 73 27 39
Ext
+33
Email
Camille.boucheny@chu-lyon.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne-Claire LUKASZEWICZ, Pr
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service civilo-militaire d'Anesthésie-Réanimation et Médecine Périopératoire
City
Lyon
ZIP/Postal Code
69003
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne-Claire LUKASZEWICZ, Pr
First Name & Middle Initial & Last Name & Degree
Anne-Claire LUKASZEWICZ, Pr
Facility Name
Service de reanimation chirurgicale Hopital Croix-Rousse
City
Lyon
ZIP/Postal Code
69004
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Charlotte DELIGNETTE, MD
Phone
4 72 11 89 47
Ext
+33
Email
marie-charlotte.delignette@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Marie-Charlotte DELIGNETTE, MD
Facility Name
Service de reanimation médicale hôpital de la Croix-Rousse
City
Lyon
ZIP/Postal Code
69004
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Christophe RICHARD, Pr
Phone
4 26 10 92 72
Ext
+33
Email
j-christophe.richard@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Jean-Christophe RICHARD, Pr
Facility Name
Service d'anesthésie-réanimation, unité de réanimation chirurgicale Picard
City
Nancy
ZIP/Postal Code
54511
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Reine Marie-Reine LOSSER, Pr
Phone
3 83 15 41 66
Ext
+33
Email
mr.losser@chru-nancy.fr
First Name & Middle Initial & Last Name & Degree
Marie-Reine LOSSER, Pr
Facility Name
Médecine intensive- Réanimation
City
Paris
ZIP/Postal Code
75014
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frederic PENE, Pr
Phone
1 58 41 25 36
Ext
+33
Email
frederic.pene@aphp.fr
First Name & Middle Initial & Last Name & Degree
Frederic PENE, Pr
Facility Name
Service d'Anesthésie-réanimation-médecine intensive Hôpital Lyon Sud
City
Pierre-Bénite
ZIP/Postal Code
69395
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Florent WALLET, MD
Phone
4 78 86 19 21
Ext
+33
Email
florent.wallet@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Florent WALLET, MD
Facility Name
Département Anesthésie-Réanimation
City
Saint-Étienne
ZIP/Postal Code
42055
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ludivine PETIT, MD
Phone
6 77 81 86 87
Ext
+33
Email
Ludivine.Petit@chu-st-etienne.fr
First Name & Middle Initial & Last Name & Degree
Ludivine PETIT, MD

12. IPD Sharing Statement

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

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