"Baricitinib for Treating Hospital-acquired Pneumonia in Critically Ill Patients With a Proinflammatory Phenotype.

The goal of this clinical trial is to determine the safety (phase II), then efficacy (phase III) of baricitinib plus standard of care (SOC) as compared to SOC alone for the treatment of hospital-acquired pneumonia in patients with a pro-inflammatory profile.

For both groups :

At inclusion visit :

* Verification of inclusion and non-inclusion criteria
* Patient information and signature of consent form
* Pregnancy test (urine ou blood)
* Randomization
* Clinical evaluation (cardiac frequency, saturation, tracheal secretions, PaO2/FiO2 ratio, body temperature, mechanical ventilation support)
* Collection of respiratory fluid and blood for biobank
* Liver function test (AST, ALT, bilirubin), blood white cells count and EKG
* Treatment compliance
* Concomitant medications (antimicrobial therapy and steriods)
* Survival and EQ-5D-5L

At visit 1 to visit 10 ( Day1- day10)

* Clinical evaluation (cardiac frequency, saturation, tracheal secretions, PaO2/FiO2 ratio, body temperature, mechanical ventilation support)
* Study drug administration (daily)
* Collection of respiratory fluid and blood for biobank (day 3 and day 7)
* Liver function test (AST, ALT, bilirubin), blood white cells count and EKG (Liver, day 3 and day 7)
* Treatment compliance
* Adverse event
* Concomitant medications (antimicrobial therapy and steriods)

At visit 11(Day 10-12 test-of-cure) :

* Clinical evaluation (cardiac frequency, saturation, tracheal secretions, PaO2/FiO2 ratio, body temperature, mechanical ventilation support)
* Collection of respiratory fluid and blood for biobank
* Collection of the respiratory fluid for bacterial cure
* Liver function test (AST, ALT, bilirubin), blood white cells count and EKG
* Adverse event
* Concomitant medications (antimicrobial therapy and steriods)

At visit 12 :

* Adverse event
* Survival and EQ-5D-5L

At visit 13 (month 3) and visit 14 (month 6) :

* Query in NHI Database (SNDS) for consumption of Health resources (pharmaceuticals, consultations...)
* Survival and EQ-5D-5L
* Health -related quality of the life (SF-36), anxiety/depression (HADS), subjective well-being (SWLS)
* Interview with a researcher in pshychology (20 patients and their relatives - only in France)

Eligibility Criteria:
Inclusion Criteria:

* Ventilators-associated pneumonia (VAP) or hospital -acquired pneumonia requiring invasive ventilation (V-HAP)
* Diagnosis of HAP according to European guidelines : association of two clinical criteria (body temperature \> 38°c and purulent pulmonary secretions), the appearance of a new infiltrate or change in an existing infiltrate on chest radography, and respiratory sample (AET, BAL, mini-BAL or blind BAL) collected for bacteriological diagnosis (results can be pending at inclusion). The diagnosis of HAP can have been made outside of ICU
* VAP : patients should have received machenical ventilation via an endotracheal or nasotracheal tube for the least 48h at the time of HAP diagnosis. V-HAP : patients should have been hospitalized for the least 48 hours before the onset of the first signs or symptoms and required invasive mechanical ventilation during HAP treatment
* Biological systemic inflammatory response defined according to the on-site standard of acre (CPR \> 125 mg/L and/or PCT \> 2µg/L and/or ferritin blood level \> 650 ng/mL
* Receiving antimicrobal therapy for the current episode of HAP pneumonia for less than 72 hours
* Informed consent from legal representative or emergency procedure (when possible according to national regulation). If it's impossible to obtain patient consent before the inclusion (comatose patients), patient consent for the study continuation will be obtained as soon as deemed possible
* Person insured under a helth insurance scheme

Exclusion Criteria:

* Pregnant women (serum or urine test), breastfeeding woment
* Patient under legal protection (inc. under guardianship or trusteesheep)
* Hypersensitivity to baricitinib
* Uncontrolled herpes zoster, viral hepatitis, infection with human immunodeficiency virus, fungal infections or tuberculosis
* Severe hepatic insufficiency (child-Pugh B or C)
* Acute or chronic renal insufficiency (modification of diet in renal disease (MDRD) creatinine clearance \< 30 ml/min/1.73 m²)
* Persistent anemia (haemoglobin \< 8 g/L), lymphopenia (absolute lymphocyte \< 500 cells/mm3)
* Immunosuppression (hematologic cancer, aplasia, chemotherapy/radiotherapy for cancer within 3 months prior to the inclusion or anti-graft rejection drug)
* Recent (\<90 days) trhomboembolic event (venous trhombosis, pulmonary embolism, myocardial infarction, and/or stroke)
* Participation to an interventional drug study within 1 month prior to the inclusion