Hospital Acquired Pneumonia
Conditions
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.
Interventions
DRUGDexamethasone
Dexamethasone phosphate injection is given as a slow injection or infusion (intravenous drip) into the veins.
DRUGPlacebo
Placebo injection is given as a slow injection or infusion (intravenous drip) into the veins.
Sponsors
Nantes University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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 \< 300 under 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 : * testing steroids or anti-graft rejection drug or chemotherapy- radiotherapy for cancer * And / Or testing a drug regimen with a known interaction with dexamethasone, * And / Or whose implementation would alter the HAP-DEX 6-month follow-up, notably the collection of the primary outcome. * Situations that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical cure rate at the test-of-cure visit (TOC visit) | Day 8-10 | It's a hierarchic procedure. First, we will test the dexamethasone superiority on the clinical cure rate at the test-of-cure visit realized 8 days (acceptable time frame Day 8-10) after randomization or at the ICU discharge (if it occurs before). |
| The rate of all-cause mortality on Day 28. | Day 28 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of death | Month 3 , Month 6 | All-cause mortality |
| Rate of pleural empyema at Day 28. | Day 28 | — |
| Rate of microbiological failure | Toc 1 day visit | — |
| Rate of pneumonia relapse | day 28 | — |
| Duration of hospitalization and hospital-free days | Month 6 | — |
| Rates of non-respiratory hospital-acquired infection | Day 28 | — |
| Antibiotic-free days at Day 28 | Day 28 | — |
| Duration of invasive mechanical ventilation and invasive mechanical ventilation-free days | Month 6 | — |
| Rate of SUSAR ( suspected unexpected serious adverse reaction) and AE ( Adverse event) | day 28 | * Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR) * Rate of metabolic adverse events |
| Rate of gastric ulcer | day 28 | — |
| Anxiety and depression were measured with the HADS (Hospital Anxiety and Depression Scale | month 3, month 6 | Changes in anxiety and depression were measured with the HADS (Hospital Anxiety and Depression Scale ) scale in order to assess the acceptability of dexamethasone from the patients' perspectives |
| Changes in subjective well-being with the Satisfaction With Life Scale (SWLS) | month 3, month 6 | Changes in subjective well-being from M3 to M6 measured with the Satisfaction With Life Scale (SWLS) in order to assess the acceptability of dexamethasone from the patients' perspectives |
| Changes in health-related quality of life measured with the Short Form (SF)-36 | month 3, month 6 | Changes in health-related quality of life with the Short Form (SF)-36 scale in order to assess the acceptability of dexamethasone from the patients' perspectives: |
| the cost-effectiveness analysis (CEA ) will estimate an incremental cost-effectiveness ratio (ICER) | month 6 | We will assess the economic efficiency of dexamethasone plus standard of care compared to standard of care by performing a cost-effectiveness analysis (CEA) using QALYs (Quality-Adjusted Life-Years) as a measure of health outcomes. the CEA will estimate an incremental cost effectiveness ratio (ICER) using a collective perspective; The ICER will be expressed in terms of costs per QALY gained. |
Countries
France, Greece, Spain
Contacts
CONTACTAntoine ROQUILLY
CONTACTLucile MARGUET
PRINCIPAL_INVESTIGATORAntoine ROQUILLY
Nantes University Hospital
Outcome results
None listed