Dexamethasone for Treating Severe Hospital-acquired Pneumonia in Critically Ill Patients With a Proinflammatory Phenotype

Hospital Acquired Pneumonia Clinical Trial

— HAP-DEX  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06269900
• Other study ID #: RC23_0358
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: February 15, 2024
• Est. completion date: August 15, 2026

Study information

• Verified date: January 2024
• Source: Nantes University Hospital
• Contact: Lucile MARGUET
• Phone: +33 2 53 48 28 76
• Email: lucile.marguet[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 450
• Est. completion date: August 15, 2026
• Est. primary completion date: March 14, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Hospital-acquired pneumonia (HAP) according to European guidelines (Torres et al. Eur Respir J 2017): Association of two clinical criteria (body temperature > 38°C 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 but at least 48 hours after hospital admission.
• 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:

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 a
• Severe septic shock (norepinephrine > 0.4 microg/kg/min and serum lactate level greater than 2 mmol/L) at the time of randomisation a
• 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, zona, varicella) or systemic fungal infectionb
• Immunosuppression (severe lymphopenia < 750 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

Related Conditions & MeSH terms

• Healthcare-Associated Pneumonia
• Hospital Acquired Pneumonia
• Pneumonia

Intervention

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

Locations

Country	Name	City	State
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 Clermont-Ferrand	Clermont-Ferrand
France	CHU Beaujon	Clichy
France	CHU Limoges	Limoges
France	CHU Marseille	Marseille
France	CHU Nancy	Nancy
France	CHU Nantes	Nantes
France	CHU Nantes (HGRL)	Nantes
France	CHU Nantes (HGRL)	Nantes
France	CHU Pitié Salpétrière	Paris
France	CHU Poitiers	Poitiers
France	CHU Rennes	Rennes
France	CHU Rennes	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical cure rate at the test-of-cure visit (TOC visit)	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).	Day 8-10
Primary	The rate of all-cause mortality on Day 28.		Day 28
Secondary	Rate of death	All-cause mortality	Month 3 , Month 6
Secondary	Rate of pleural empyema at Day 28.		Day 28
Secondary	Rate of microbiological failure		Toc 1 day visit
Secondary	Rate of pneumonia relapse		day 28
Secondary	Duration of hospitalization and hospital-free days		Month 6
Secondary	Rates of non-respiratory hospital-acquired infection		Day 28
Secondary	Antibiotic-free days at Day 28		Day 28
Secondary	Duration of invasive mechanical ventilation and invasive mechanical ventilation-free days		Month 6
Secondary	Rate of SUSAR ( suspected unexpected serious adverse reaction) and AE ( Adverse event)	Rate of serious adverse reactions and suspected unexpected serious adverse reaction (SUSAR); Rate of metabolic adverse events	day 28
Secondary	Rate of gastric ulcer		day 28
Secondary	Anxiety and depression were measured with the HADS (Hospital Anxiety and Depression Scale	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	month 3, month 6
Secondary	Changes in subjective well-being with the Satisfaction With Life Scale (SWLS)	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	month 3, month 6
Secondary	Changes in health-related quality of life measured with the Short Form (SF)-36	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:	month 3, month 6
Secondary	the cost-effectiveness analysis (CEA ) will estimate an incremental cost-effectiveness ratio (ICER)	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.	month 6