DEXAMETHASONE PHOSPHATE for Hospital-acquired pneumonia

Inclusion criteria

• {"criterion_text":"-Adult patients (18yr to 85yr)"}
• {"criterion_text":"-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."}
• {"criterion_text":"-HAP severity defined as a PaO2/FiO2 ratio < 300 under mechanical ventilation."}
• {"criterion_text":"-Biological systemic inflammatory response defined as CPR≥ 150 mg/L (15 mg/dL)"}
• {"criterion_text":"-Receiving curative antimicrobial therapy for the current episode of HAP pneumonia for less than 48 hours."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Person insured under a health insurance scheme."}
• {"criterion_text":"-Female of childbearing age who agree and who are able to comply with effective contraception for the 28 first days of the study: sexual abstinence, use of a condom with spermicide, contraceptive sponge, uterine diaphragm, hormonal contraception, or intrauterine contraceptive device"}

Exclusion criteria

• {"criterion_text":"-Pregnant women (serum or urine test), breastfeeding women."}
• {"criterion_text":"-Uncontrolled psychotic disorder (acute or chronical)"}
• {"criterion_text":"-Patients not expected to survive for more than 48 hours"}
• {"criterion_text":"-Severe septic shock (norepinephrine > 0.4 microg/kg/min and serum lactate level greater than 2 mmol/L) at the time of randomisation"}
• {"criterion_text":"-Patient under legal protection (incl. under guardianship or trusteeship)."}
• {"criterion_text":"-Hypersensitivity to dexamethasone and hypersensitivity to all of its excipients"}
• {"criterion_text":"-Ongoing administration of glucocorticoid at the time of randomisation."}
• {"criterion_text":"-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"}
• {"criterion_text":"-Uncontrolled viral (hepatitis, zona,herpes, varicella) or systemic fungal infection"}
• {"criterion_text":"-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)."}

Primary endpoints

• {"endpoint_text":"-The co-primary hierarchic endpoints to demonstrate the efficacy of dexamethasone plus SOC compared to placebo plus SOC for the treatment of hospital-acquired pneumonia will be a clinical cure at the test-of-cure (TOC) visit and all-cause mortality at Day 28.","definition_or_measurement_approach":"Clinical cure assessed at the test-of-cure (TOC) visit; all-cause mortality measured at Day 28."}

Secondary endpoints

• {"endpoint_text":"-In case of a non-significant difference in the rate of clinical cure, the co-primary outcome (all-cause mortality at Day 28) will be presented as a secondary outcome.","definition_or_measurement_approach":""}
• {"endpoint_text":"-All-cause mortality at Month 3 and Month 6.","definition_or_measurement_approach":"All-cause mortality assessed at Month 3 and Month 6."}
• {"endpoint_text":"-Rate of pleural empyema at Day 28.","definition_or_measurement_approach":"Occurrence of pleural empyema assessed by Day 28."}
• {"endpoint_text":"-Rate of microbiological failure (defined as a positive respiratory culture at the ToC visit).","definition_or_measurement_approach":"Microbiological failure defined as positive respiratory culture at TOC visit."}
• {"endpoint_text":"-Rate of pneumonia relapse (defined as a second episode of HAP with one or more identical pathogens), rate of pneumonia recurrence (defined as a second episode of HAP with different pathogens) at Day 28.","definition_or_measurement_approach":"Relapse: second HAP episode with identical pathogen(s); recurrence: second HAP with different pathogen(s); measured at Day 28."}
• {"endpoint_text":"-Time course of body temperature, cardiac pulse rate, oxygen saturation, PaO2/FiO2, type of mechanical ventilation support (invasive, noninvasive, none) (daily evaluation at 8.00 am and 8.00 pm), and leukocyte counts (every 48 hours) for 10 days.","definition_or_measurement_approach":"Daily assessments as specified (twice daily vitals; leukocyte counts every 48 hours) from Day 0 to Day 10."}
• {"endpoint_text":"-Rates of non-respiratory hospital-acquired infection at day 28: urinary tract infection, surgical site infection, invasive candidiasis, septicemia.","definition_or_measurement_approach":"Incidence of specified non-respiratory nosocomial infections by Day 28."}
• {"endpoint_text":"-Antibiotic-free days at Day 28 (the number of antibiotic-free days is defined as the number of days between Day 1 and Day 28 for which living patients do not receive antibiotics. Dead patients will be ascribed 0 antibiotic-free days).","definition_or_measurement_approach":"Count of days alive and antibiotic-free between Day 1 and Day 28; deceased patients = 0 antibiotic-free days."}
• {"endpoint_text":"-Duration of invasive mechanical ventilation and invasive mechanical ventilation-free days at Month 6 (defined as the number of days between Day 1 and Month 6 for which living patients breathe spontaneously. Dead patients will be ascribed 0 mechanical ventilation-free days).","definition_or_measurement_approach":"Duration measured until Month 6; ventilation-free days counted as days alive and spontaneously breathing between Day 1 and Month 6; deceased = 0."}
• {"endpoint_text":"-Duration of hospitalization and hospital-free days at Month 6 (the number of hospital-free days is defined as the number of days between Day 1 and Month 6 for which living patients are outside of a hospital. Dead patients will be ascribed 0 hospital-free days).","definition_or_measurement_approach":"Hospital-free days counted between Day 1 and Month 6; deceased = 0."}
• {"endpoint_text":"-Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR) at Day 28.","definition_or_measurement_approach":"Incidence of serious adverse reactions and SUSARs up to Day 28."}
• {"endpoint_text":"-Rate of metabolic adverse events during the 5-7-day treatment period (number of days with a blood level of potassium < 3.5 mmol/l, number of days with of sodium < 135 mmol/l, daily dose of insulin).","definition_or_measurement_approach":"Number of days with specified metabolic abnormalities during treatment period; daily insulin dose recorded."}
• {"endpoint_text":"-Rate of gastric ulcer.","definition_or_measurement_approach":"Incidence of gastric ulcer during follow-up."}
• {"endpoint_text":"-Economic endpoints at 6 months: Incremental cost-effectiveness ratio (ICER)","definition_or_measurement_approach":"ICER calculated at 6 months comparing dexamethasone+SOC vs placebo+SOC."}
• {"endpoint_text":"-Changes in health-related quality of life (HRQoL) from three (M3) to six months (M6) after randomization measured with the Short Form (SF)-36 scale validated in French","definition_or_measurement_approach":"Change in SF-36 scores from M3 to M6."}
• {"endpoint_text":"-Changes in anxiety and depression from M3 to M6 were measured with the HADS scale validated in French","definition_or_measurement_approach":"Change in HADS scores from M3 to M6."}
• {"endpoint_text":"-Changes in subjective well-being from M3 to M6 measured with the Satisfaction With Life Scale (SWLS) validated in French","definition_or_measurement_approach":"Change in SWLS scores from M3 to M6."}
• {"endpoint_text":"-Rates of major cardiovascular events at Day 28: subsegmental pulmonary embolism, stroke, myocardial infarction (positive ST segment).","definition_or_measurement_approach":"Incidence of specified major cardiovascular events by Day 28."}

France

Earliest CTIS Part Ii Submission Date

11-12-2023

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

809

Number Of Sites

29

Number Of Participants

450

Belgium

Earliest CTIS Part Ii Submission Date

27-05-2025

Latest Decision Or Authorization Date

24-02-2026

Processing Time Days

269

Number Of Sites

3

Number Of Participants

27

Greece

Earliest CTIS Part Ii Submission Date

16-06-2025

Latest Decision Or Authorization Date

25-02-2026

Processing Time Days

254

Number Of Sites

5

Number Of Participants

60

Spain

Earliest CTIS Part Ii Submission Date

30-06-2025

Latest Decision Or Authorization Date

02-03-2026

Processing Time Days

245

Number Of Sites

3

Number Of Participants

60

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Nantes

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Contract research organisations

Name

Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.

Responsibilities

Sign contracts with participating sites or other sub-contracting parties on behalf of the Sponsor, and perform relevant payments.; other sponsor duties listed in record.

Third parties

• {"country":"Greece","full_name":"Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.","duties_or_roles":"Sign contracts with participating sites or other sub-contracting parties on behalf of the Sponsor, and perform relevant payments.; other duties codes listed (1,12,5).","organisation_type":"Pharmaceutical company"}