Clinical trial NCT05914584: "Baricitinib for Treating Hospital-acquired Pneumonia in Critically Ill Patients With a Proinflammatory Phenotype.
Official title: "Baricitinib for Treating Hospital-acquired Pneumonia in Critically Ill Patients With a Proinflammatory Phenotype, an International Phase II/Phase III, Randomized, Controlled Trial - TREAT-HAP Study.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Hospital-acquired Pneumonia
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2023-06-22
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: Determine the safety (phase II), 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
timeFrame: Day 28
measure: Determine the 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
timeFrame: Day 28
Secondary outcomes:
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity
timeFrame: Month 3 and Month 6
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality
timeFrame: Month 3 and Month 6
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity reduction
timeFrame: Up to 28 days
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Up to 28 days
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Up to Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Up to Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Up to Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Up to Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Up to Day 12
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Day 28
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity reduction
timeFrame: Up to Month 3
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Up to Month 3
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated mortality reduction
timeFrame: Up to Month 3
measure: To demonstrate the efficacy of baricitinib on pneumonia-associated morbidity reduction
timeFrame: Up to Month 3
Other outcomes:
measure: Determine the safety of baricitinib
timeFrame: Day 10-12
measure: Determine if baricitinib increases the economic efficiency of the treatment of pneumonia
timeFrame: 6 months
measure: Determine the suitability of baricitinib from the patient's perspectives
timeFrame: Up to 6 months
measure: Determine the suitability of baricitinib from the patient's perspectives
timeFrame: Up to 6 months
measure: Determine the suitability of baricitinib from the patient's perspectives
timeFrame: Up to 6 months
measure: To identify biomarkers for stratidication of patents into responders and non-responders to baricitinib
timeFrame: Day 10-12
measure: To identify a biobank of blood and respiratory samples collected from humans with hospital-acquired pneumonia
timeFrame: Day 10-12
measure: Determine the safety of baricitinib
timeFrame: Day 28
measure: Determine the safety of baricitinib
timeFrame: Day 10-12
measure: Determine the safety of baricitinib
timeFrame: Day 10-12
measure: Determine the safety of baricitinib
timeFrame: Day 10-12
measure: Determine the safety of baricitinib
timeFrame: Day 10-12
measure: Determine the safety of baricitinib
timeFrame: Day 10-12
Locations:
city: Bruxelles
country: Belgium
facility: St-Luc Clinics
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Haine-Saint-Paul
country: Belgium
facility: Groupe Jolimont
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Yvoir
country: Belgium
facility: University Hospital of UCL Namur
city: Angers
country: France
facility: CHU Angers
city: Brest
country: France
facility: CHU de Brest
city: Caen
country: France
facility: CHU de Caen
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: La Roche-sur-Yon
country: France
facility: CH La Roche sur Yon
city: Limoges
country: France
facility: CHU de Limoges
city: Marseille
country: France
facility: CHU de Marseille
city: Nancy
country: France
facility: CHU de Nancy
city: Nantes
country: France
facility: CHU de Nantes
city: Nantes
country: France
facility: CHU de Nantes
city: Nantes
country: France
facility: CHU de Nantes
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: CHU de Beaujon
city: Paris
country: France
facility: CHU la Pitié-Salpétrière
city: Paris
country: France
facility: CHU Pitié-Salpétrière
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rennes
country: France
facility: CHU de Rennes
city: Rennes
country: France
facility: CHU de Rennes
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelone
country: Spain
facility: Hospital Clinic
Study officials:
affiliation: Nantes University Hospital
name: Antoine ROQUILLY
role: PRINCIPAL_INVESTIGATOR
References: