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

August 5, 2025 updated by: Nantes University Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

450

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: dexamethasone + standard of care
  • 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 < 300).
  • 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.
Drug: Dexamethasone
Dexamethasone phosphate injection is given as a slow injection or infusion (intravenous drip) into the veins.
Placebo Comparator: Placebo + Standard of care
  • 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 < 300).
  • 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.
Drug: Placebo
Placebo injection is given as a slow injection or infusion (intravenous drip) into the veins.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical cure rate at the test-of-cure visit (TOC visit)
Time Frame: 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).
Day 8-10
The rate of all-cause mortality on Day 28.
Time Frame: Day 28
Day 28

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nantes University Hospital

Investigators

  • Principal Investigator: Antoine Roquilly, Nantes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2024

Primary Completion (Estimated)

March 14, 2026

Study Completion (Estimated)

August 15, 2026

Study Registration Dates

First Submitted

February 5, 2024

First Submitted That Met QC Criteria

February 20, 2024

First Posted (Actual)

February 21, 2024

Study Record Updates

Last Update Posted (Actual)

August 11, 2025

Last Update Submitted That Met QC Criteria

August 5, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC23_0358

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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