Clinical trial NCT06269900: Dexamethasone for Treating Severe Hospital-acquired Pneumonia in Critically Ill Patients With a Proinflammatory Phenotype
Official title: Dexamethasone for Treating Severe Hospital-acquired Pneumonia in Critically Ill Patients With a Proinflammatory Phenotype, an International Phase III, Double-blind, Placebo-controlled, Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hospital Acquired Pneumonia
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2024-02-21
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: Determine the efficacy of dexamethasone plus standard of care (SOC) as compared to placebo plus SOC for treating severe hospital-acquired pneumonia in critically ill patients with a proinflammatory phenotype; It's an international phase III, double-blind, placebo-controlled, randomized trial.


Eligibility criteria: Inclusion Criteria:

* Hospital-acquired pneumonia (HAP) according to European guidelines (Torres et al. Eur Respir J 2017): Association of two criteria among (body temperature \> 38°C, leukocytosis\>12000 cells per mL, leucopenia \<4000 cells per mL and purulent pulmonary secretions), appearance of a new infiltrate or change in an existing infiltrate on chest radiography, and respiratory sample (Sputum, 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. Diagnosis is done at least 48 hours after hospital admission.
* HAP severity defined as a PaO2/FiO2 ratio \< 200 under invasive mechanical ventilation.
* Biological systemic inflammatory response defined as CPR\> 150 mg/L (15 mg/dL)\*
* Receiving curative antimicrobial therapy for the current episode of HAP pneumonia for less than 48 hours.
* Informed consent from a legal representative, or emergency procedure (when possible, according to national regulation, see below). If it is not possible to obtain the patient consent prior the inclusion (comatose patients), patient consent for the study continuation will be obtained as soon as deemed possible.
* Person insured under a health insurance scheme.
* Female of childbearing age who agree and who are able to comply with effective contraception for the 28 first days of the study:

Exclusion Criteria:

* Pregnant women (serum or urine test), breastfeeding women.
* Patient under legal protection (incl. under guardianship or trusteeship).
* Hypersensitivity to dexamethasone and hypersensitivity to all of its excipients
* Ongoing administration of glucocorticoid at the time of randomisation, such as for COVID-19 infection requiring supplemental oxygen therapy
* Severe septic shock (norepinephrine \> 0.4 microg/kg/min and serum lactate level greater than 2 mmol/L) at the time of randomisation
* Prolonged use of corticosteroids at a mean minimum dose of 0.3 mg/kg/day of prednisone equivalent for \>3 weeks in the past 60 days
* Uncontrolled viral (hepatitis,herpes, zona, varicella) or systemic fungal infection
* Immunosuppression pre-existing to hospitalisation (severe lymphopenia \< 500 lymphocytes/mm3, hematologic cancer, aplasia, chemotherapy/radiotherapy for cancer within 3 months prior to the inclusion, or anti-graft rejection drug).
* Uncontrolled psychotic disorder (acute or chronical)
* Patients not expected to survive for more than 48 hours.
* Participation in another drug clinical trial

Primary outcomes:
measure: Clinical cure rate at the test-of-cure visit (TOC visit)
timeFrame: Day 8-10
measure: The rate of all-cause mortality on Day 28.
timeFrame: Day 28
Secondary outcomes:
measure: Rate of death
timeFrame: Month 3 , Month 6
measure: Rate of pleural empyema at Day 28.
timeFrame: Day 28
measure: Rate of microbiological failure
timeFrame: Toc 1 day visit
measure: Rate of pneumonia relapse
timeFrame: day 28
measure: Duration of hospitalization and hospital-free days
timeFrame: Month 6
measure: Rates of non-respiratory hospital-acquired infection
timeFrame: Day 28
measure: Antibiotic-free days at Day 28
timeFrame: Day 28
measure: Duration of invasive mechanical ventilation and invasive mechanical ventilation-free days
timeFrame: Month 6
measure: Rate of SUSAR ( suspected unexpected serious adverse reaction) and AE ( Adverse event)
timeFrame: day 28
measure: Rate of gastric ulcer
timeFrame: day 28
measure: Anxiety and depression were measured with the HADS (Hospital Anxiety and Depression Scale
timeFrame: month 3, month 6
measure: Changes in subjective well-being with the Satisfaction With Life Scale (SWLS)
timeFrame: month 3, month 6
measure: Changes in health-related quality of life measured with the Short Form (SF)-36
timeFrame: month 3, month 6
measure: the cost-effectiveness analysis (CEA ) will estimate an incremental cost-effectiveness ratio (ICER)
timeFrame: month 6
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens
city: Angers
country: France
facility: CHU Angers
city: Bordeaux
country: France
facility: Chu Bordeaux
city: Bordeaux
country: France
facility: Chu Bordeaux
city: Brest
country: France
facility: CHU Brest
city: Caen
country: France
facility: CHU Caen
city: Clermont-Ferrand
country: France
facility: CHU Clermont - Ferrand
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Clichy
country: France
facility: CHU Beaujon
city: Garches
country: France
facility: CHU Raymond Poincaré
city: Grenoble
country: France
facility: Chu Grenoble
city: Limoges
country: France
facility: CHU Limoges
city: Marseille
country: France
facility: CHU Marseille
city: Nancy
country: France
facility: Chu Nancy
city: Nantes
country: France
facility: CHU Nantes (HGRL)
city: Nantes
country: France
facility: CHU Nantes
city: Nantes
country: France
facility: CHU Nantes (HGRL)
city: Nimes
country: France
facility: Chu Nimes
city: Paris
country: France
facility: CHU Pitié Salpétrière
city: Paris
country: France
facility: CHU Pitié Salpétrière
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes
city: Rennes
country: France
facility: CHU Rennes
city: Strasbourg
country: France
facility: Chu Strasbourg
city: Toulouse
country: France
facility: Chu Toulouse
Study officials:
affiliation: Nantes University Hospital
name: Antoine ROQUILLY
role: PRINCIPAL_INVESTIGATOR
References: