Patients hospitalized in intensive care units, under mechanical ventilation MedDRA version: 21.1 Level: PT Classification code 10022519 Term: Intensive care System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 20.0 Level: LLT Classification code 10076918 Term: Hospital acquired pneumonia System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Imukin
Pharmaceutical Form: Solution for injection
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use
Sponsors
Nantes University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adult patients (18yr to 85yr). - Hospitalized in intensive care unit for less than 48 hours. - Receiving invasive mechanical ventilation at the time of inclusion. - One or more acute organ failure at the time of inclusion among: neurological (Glasgow coma scale 2 fold higher than the basal value and/or oliguria =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: • Pregnant women (serum or urine test), breastfeeding women • Patient under legal protection (incl. under guardianship or trusteeship) • 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 • Severe hepatic insufficiency (Child Pugh score B or C) • Liver cytolysis with hepatic enzymes (AST and/or ALT) > 5N) • Severe chronic renal insufficiency (MDRD Creatinine Clearance 5 mmol/L.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to determine whether rHu-IFN-? as compared with placebo, could reduce the rate of hospital-acquired pneumonia and improve outcomes in patients admitted to intensive care unit and requiring mechanical ventilation. ;Secondary Objective: • to demonstrate the efficiency of rHuIFN-?, on pneumonia-associated morbidity and mortality reduction • to demonstrate the efficiency of rHuIFN-? on antimicrobial therapy utilization reduction • To describe the safety and tolerability of rHu-IFN-? • To assess the suitability, acceptability, and adaptability of rHu-IFN-? • To assess the economic efficiency of rHuIFN-? for the prevention of pneumonia • To develop biomarkers for the stratification of patients into responders and non-responders of rHuIFN-? • To develop a biobank of blood and respiratory samples collected in humans at risk of hospital-acquired pneumonia ;Primary end point(s): To demonstrate the efficiency of rHuIFN-? for the prevention of hospital-acquired pneumonia, the primary endpoint is the composite outcome of all-cause mortality at day 28 and/or the occurrence of hospital-acquired pneumonia within 28 days after randomization. Hospital acquired-pneumonia is diagnosed after the 48th hour of hospitalization according to European and French guidelines (Torres et al. Eur Respir J 2017; Leone et al. ACCPM 2018) : - at least two of the following criteria: body temperature >38°C; leucocytosis>12000 cells per mL, leucopenia 48h. Respiratory samples are obtained before starting any new antibiotic treatment. An adjudication committee, composed of 1 investigator by country who will be blinded to the trial-group assignments, will review the medical charts of patients with respiratory tract infections of the 2 other participating countries, in order to review the diagnosis. ;Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcomes to determine the efficiency of rHu-IFN-?, on pneumonia-associated morbidity and mortality reduction are: -All-cause mortality at D28 and 90. -Hospital acquired Pneumonia at D28 -Bacterial ecology of the 1st episode of HAP (respiratory fluids). -Rate of ventilator-associated tracheobronchitis at D28 defined as at least two of the following criteria : body temperature >38°C; leukocytosis>12000 cells per mL, leucopenia <4000 cells per mL, or purulent pulmonary secretions and a positive culture of a respiratory tract samples, without appearance of a new infiltrate or change in an existing infiltrate on chest radiography (Martin-Loeches et al. Lancet Respir Med 2015) -Acute Respiratory Distress Syndrome within 28d after randomization -Duration of antimicrobial therapy at D28, antibiotic free days at D28 (the number of antibiotic free days is defined as the number of days between D1 and D28 for which living patients don’t receive antibiotics. Dead patients will be ascribed 0 antibiotic free days). -Duration of mechanical ventilation at D90, mechanical ventilation free days at D90. -Duration of ICU hospitalization at D90, Duration of hospitalization at D90, hospital free days at D90. The secondary outcomes to determine the tolerance of rHu-IFN-? are: -Rate of serious adverse effects and suspected unexpected serious adverse reaction (SUSAR) at D15. -Rate of leukocytosis, neutropenia, lymphopenia, thrombopenia at D15. -Rate of liver cytolysis (Increases in AST and/or ALT) at D15. -Rate of pancreatitis (Increase in Lipase) at D15. -Fever,headache,nausea at D15. -Allergic reaction at D15. -Injection site reaction at D15. -Myalgia, arthralgia, back pain at D15. The secondary outcomes to determine the economic efficiency of rHu-IFN-? in the prevention of pneumonia are: Economic endpoints at M3:Incremental cost effectiveness ratio (ICER). We will assess the economic efficiency of the various interventions compared by performing a | — |
Countries
France
Contacts
Public ContactClinical Research Department
Nantes University Hospital
Outcome results
None listed