Severe community-acquired pneumonia MedDRA version: 18.0 Level: LLT Classification code 10010120 Term: Community acquired pneumonia System Organ Class: 100000004862
Conditions
Interventions
Trade Name: HYDROCORTISONE UPJOHN 100 mg for injection
Product Name: HYDROCORTISONE
Pharmaceutical Form: Powder and solvent for solution for infusion
Pharmaceutical form of the placebo: Powder and so
Sponsors
CHRU de TOURS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age = 18 years • Admission to an ICU or intermediate care unit participating to the trial • Diagnosis of CAP suggested by at least two of the following : cough, purulent sputum, chest pain and dyspnea • Focal shadowing/infiltrate on chest X-ray or CT-scan • Diagnosis of CAP during the 48 hours post-hospital admission • Study drug infusion initiated no longer than 24 hours post first severity criterion • Severity defined by at least one of the following : - Pneumonia Severity Index (PSI) > 130 (Fine class V) - Patient placed on mechanical ventilation (invasive or not) for acute respiratory failure, with a PEEP level of 5 cm of water or more - Patient treated by high-flow oxygen therapy with a FiO2 of 50% or more and a P/F ratio lower than 200 • Patient already treated by antibiotics (at least one dose) • Patients affiliated to social security scheme (“Sécurité sociale”) • Informed consent signed by the patient, its relatives or emergency procedure Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 600 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 600
Exclusion criteria
Exclusion criteria: • Patient treated by vasopressors for septic shock at the time of inclusion • Clinical history suggesting of aspiration of gastric content • Patient treated by invasive mechanical ventilation within 14 days before current hospital admission • Patient treated by antibiotics for a respiratory infection for more than five days at the admission to the hospital (except if a pathogen resistant to this antibiotics is isolated) • History of cystic fibrosis • Post-obstructive pneumonia • Patients in which rapid PCR-test is positive for flu • Active tuberculosis or fungal infection • Active viral hepatitis or active infection with herpes viruses • Decision of withholding mechanical ventilation or endotracheal intubation • Patient needing anti-inflammatory corticosteroids or substitutive hydrocortisone for any reason. • Patients under treatment by more than 15 mg/d of prednisone (or equivalent) for more than 30 days • Patient already enrolled in another drug trial • Pregnant or breastfeeding woman • Patient on judicial protection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Demonstrate that hydrocortisone started during the first 24 hours following the occurrence of the first severity criterion and administered for four to seven day at full dose (and then tapered for another four or seven days period) to patients admitted to the ICU for severe CAP could improve the D-28 survival when compared to placebo.;Secondary Objective: • Demonstrate that hydrocortisone could decrease: - The need for intubation (for patients not-intubated at inclusion) - The need for non-invasive ventilation (for patients not-ventilated at inclusion) - The length of mechanical ventilation - The need for vasopressors - The vasopressors length of administration - The ICU and/or intermediate care unit length-of-stay (LOS) - The D-90 mortality - The level/activity of inflammation biomarkers • Demonstrate that hydrocortisone could improve: - The oxygenation parameters - The level of organ dysfunctions - The survivors quality of life • Evaluate the side-effects potentially linked to CTx administration in this clinical setting;Primary end point(s): D28 all causes mortality;Timepoint(s) of evaluation of this end point: D28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • In patients non-invasively ventilated at inclusion, proportion of patients needing endotracheal intubation • In patients non-ventilated at inclusion, proportion of patients requiring non-invasive ventilation (NIV) and proportion of patients needing endotracheal intubation • D28 ventilator-free-days. This outcome will be assessed applying the following rules: - The period of interest will begin at the randomization date - Patients who die before day 28 will be affected a 0 value - Days between two mechanical ventilation episodes will be taken into account - A successful extubation will be defined as a spontaneous breathing 48h after extubation • Number of patients with vasopressor therapy initiation from inclusion to D28 • D28 vasopressor-free-days. This outcome will be assessed applying the following rules: - The period of interest will begin at the randomization date - Patients who die before day 28 will be affected a 0 value - Days between two vasoconstrictor-therapy episodes will be taken into account • ICU and/or intermediate care unit LOS • All-causes mortality at D90 • SF-36 Health Survey at D90 • Biomarkers : procalcitonin, C-reactive protein and plasmatic concentration of pro-inflammatory cytokines (IL-6, IL-20, IL-22, IL-22BP, HBD2, TNF alpha) at baseline, D3 and D7 • P/F ratio measured daily from D1 to D7, at the end of treatment, at the end of ICU-stay and/or D28 • SOFA calculated daily from D1 to D7, at the end of treatment, at the end of ICU-stay and/or D28 • Proportion of patients experiencing secondary infection during their ICU-stay • Proportion of patients experiencing gastrointestinal bleeding during their ICU-stay • Daily amount of insulin administered to the patient from D1 to D7 • Weight-gain from baseline to D7 ;Timepoint(s) of evaluation of this end point: Baseline, D1 to D7, at the end of treatment, at the end of ICU-stay, D28, D90 | — |
Countries
France
Contacts
Public ContactClinical Research Asssociate
CHRU de TOURS
Outcome results
None listed