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

Overview

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

• Drug Dexamethasone
  Dexamethasone phosphate injection is given as a slow injection or infusion (intravenous drip) into the veins.
• Drug Placebo
  Placebo injection is given as a slow injection or infusion (intravenous drip) into the veins.

Primary outcome measures

• Clinical cure rate at the test-of-cure visit (TOC visit) [Time frame: Day 8-10]
• The rate of all-cause mortality on Day 28. [Time frame: Day 28]

Secondary outcome measures (12)

• Rate of death [Time frame: Month 3 , Month 6]
• Rate of pleural empyema at Day 28. [Time frame: Day 28]
• Rate of microbiological failure [Time frame: Toc 1 day visit]
• Rate of pneumonia relapse [Time frame: day 28]
• Duration of hospitalization and hospital-free days [Time frame: Month 6]
• Rates of non-respiratory hospital-acquired infection [Time frame: Day 28]
• Antibiotic-free days at Day 28 [Time frame: Day 28]
• Duration of invasive mechanical ventilation and invasive mechanical ventilation-free days [Time frame: Month 6]
• Rate of SUSAR ( suspected unexpected serious adverse reaction) and AE ( Adverse event) [Time frame: day 28]
• Rate of gastric ulcer [Time frame: day 28]
• Anxiety and depression were measured with the HADS (Hospital Anxiety and Depression Scale [Time frame: month 3, month 6]
• Changes in subjective well-being with the Satisfaction With Life Scale (SWLS) [Time frame: month 3, month 6]

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 < 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

France · 26 centers

• Chu Amiens — Amiens
• CHU Angers — Angers
• Chu Bordeaux — Bordeaux
• Chu Bordeaux — Bordeaux
• CHU Brest — Brest
• CHU Caen — Caen
• CHU Clermont - Ferrand — Clermont-Ferrand
• CHU Clermont-Ferrand — Clermont-Ferrand
• … and 18 more centers

Identifiers

NCT: NCT06269900 · RC23_0358

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗