Dexamethasone for Treating Severe Hospital-acquired Pneumonia in Critically Ill Patients With a Proinflammatory Phenotype
- Registration Number
- NCT06269900
- Lead Sponsor
- Nantes University Hospital
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 450
- 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:
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description dexamethasone + standard of care Dexamethasone * Dexamethasone 0.2mg.kg-1.day-1 intravenous for a minimal duration of 5 days, and a maximal duration of 7 days in case of persistence of ARDS criteria (PaO2/FiO2 ratio \< 200). * Standard of care: antimicrobial therapy in compliance with European guidelines. Briefly, intravenous antimicrobial therapy with the narrowest spectrum to cover at-risk and/or identified pathogens for 7-8 days. Placebo + Standard of care Placebo * Placebo 0.2mg.kg-1.day-1 intravenous for 5 days and a maximal duration of 7 days in case of persistence of ARDS criteria (PaO2/FiO2 ratio \< 200). * Standard of care: antimicrobial therapy in compliance with European guidelines. Briefly, intravenous antimicrobial therapy with the narrowest spectrum to cover at-risk and/or identified pathogens for 7-8 days.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Rate of pleural empyema at Day 28. Day 28 Rate of microbiological failure Toc 1 day visit Duration of hospitalization and hospital-free days Month 6 Rates of non-respiratory hospital-acquired infection Day 28 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 eventsAnxiety 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
Rate of death Month 3 , Month 6 All-cause mortality
Rate of pneumonia relapse 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 gastric ulcer day 28 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.
Trial Locations
- Locations (21)
Chu Amiens
🇫🇷Amiens, France
Chu Bordeaux
🇫🇷Bordeaux, France
CHU Raymond Poincaré
🇫🇷Garches, France
Chu Grenoble
🇫🇷Grenoble, France
Chu Nancy
🇫🇷Nancy, France
Chu Nimes
🇫🇷Nimes, France
Chu Strasbourg
🇫🇷Strasbourg, France
Chu Toulouse
🇫🇷Toulouse, France
CHU Angers
🇫🇷Angers, France
CHU Brest
🇫🇷Brest, France
CHU Caen
🇫🇷Caen, France
CHU Clermont - Ferrand
🇫🇷Clermont-Ferrand, France
CHU Clermont-Ferrand
🇫🇷Clermont-Ferrand, France
CHU Beaujon
🇫🇷Clichy, France
CHU Limoges
🇫🇷Limoges, France
CHU Marseille
🇫🇷Marseille, France
CHU Nantes (HGRL)
🇫🇷Nantes, France
CHU Poitiers
🇫🇷Poitiers, France
CHU Rennes
🇫🇷Rennes, France
CHU Nantes
🇫🇷Nantes, France
CHU Pitié Salpétrière
🇫🇷Paris, France