Clinical Trials in France / NCT06916481
Recruiting
Observational
Definition of Sub-phenotypes of Pneumonia Based on the Respiratory Microbiome Composition to Predict Microbial and Clinical Treatment Failures
NCT06916481 · tracked via the Priya Life Science France tracker
Condition(s) studied
Community Acquired or Acquiring Hospital Acquired Pneumonia
Study summary
Background: Pneumonia remains a leading cause of antibiotic consumption globally, contributing significantly to the burden of antimicrobial resistance (AMR). The respiratory microbiome plays a crucial role in the emergence of AMR and therapeutic failure in both community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). The PHENOMENON study aims to investigate the relationship between the respiratory microbiome composition and clinical outcomes to improve the prediction of treatment failure and AMR emergence.
Methods: This multicenter prospective cohort study will include 300 adult patients across three cohorts: CAP in general wards, severe CAP in intensive care units (ICU), and ventilator-associated HAP (vHAP/VAP). Patients will undergo oropharyngeal and rectal swabbing at admission (Day 0), Day 3, Day 7-10, and Day 90, along with blood sampling and endotracheal aspirates in intubated patients. The primary objective is to assess the association between baseline respiratory microbiome composition and time to antibiotic response within 7-10 days. The composite primary endpoint includes clinical failure, microbiological failure, or AMR emergence. Secondary endpoints explore the association between microbiome composition and pneumonia recurrence, severity, hospital length of stay, and mortality at Day 28 and Day 90.
Expected Outcomes: This study will provide insights into the predictive value of respiratory microbiome composition on antibiotic response and AMR emergence. Understanding these relationships may guide personalized antibiotic strategies and optimize pneumonia management, ultimately reducing treatment failure rates and improving patient outcomes.
Eligibility
Inclusion Criteria:
* Cohort 1: CAP at emergency department and requiring hospitalization in general wards :
* Age ≥18 years
* Hospitalization in a medical department (not ICU)
* Presence of at least one acute clinical sign compatible with pneumonia (e.g. dyspnea, cough, purulent sputum or purulent tracheal aspirations or crackles), and temperature above 38°C in the 48 hours prior to inclusion
* AND new pulmonary infiltrate on chest X-ray or CT scan (on Day 0 or within three days of inclusion)
* Efficient treatment initiated for less than 24 hours
* Sputum collection possible
* Cohort 2: Severe CAP with ICU hospitalization :
* Age ≥18 years
* Hospitalization in intensive care unit for at least 24 hours.
* Presence of at least one acute clinical sign compatible with pneumonia (e.g. dyspnoea, cough, purulent sputum or crackles), temperature greater than 38°C in the 48 hours prior to hospital admission
* AND new pulmonary infiltrate on chest X-ray or CT scan (on Day 0 or within three days of inclusion)
* Efficient treatment initiated for less than 24 hours
* Sputum collection or tracheal aspiration or any distal bacterial sample (BAL, plugged telescopic catheter) collection possible
* Cohort 3: vHAP or VAP :
* Age ≥18 years
* vHAP: mechanical ventilation, in a patient previously hospitalized for more than 48 hours at the onset of new or worsening radiological infiltrates and 2 of the following: fever or hypothermia, leukocytosis \> 12 G/L or leukopenia \< 4G/L, purulent tracheal aspirates,
* VAP: mechanical ventilation for more than 48 hours, new or worsening radiological infiltrates and 2 of the following: fever (\>38°C) or hypothermia (\<36.5°C) in the 24 hours prior to inclusion, leucocytosis\> 12 G/L or leukopenia \< 4G/L, purulent tracheal aspirates
* AND plugged telescopic catheter (PTC) ≥103colony-forming units (CFU)/ml or bronchoalveolar lavage (BAL) culture ≥104 CFU/ml or purulent tracheal aspirates ≥ 106 UFC/mL
* AND treated with active antibiotic therapy for pneumonia for less than 24 hours
Exclusion Criteria:
* Cohort 1: CAP with hospitalization in general wards :
* AIDS
* Patient on high-dose corticosteroids \>2 mg/kg prednisone equivalent
* Bone marrow transplant patients
* Cancer patients undergoing chemotherapy within 3 months of inclusion
* Opposition of the patient (absence of informed written consent)
* Scheduled transfer to another hospital
* Patient under guardianship or comparable legal status
* NB: Patients included in the cohort 1 and referred to ICU within the first 24 hours will be included in the cohort 2.
* Cohort 2: Severe CAP with ICU hospitalization :
* AIDS
* Patient on high-dose corticosteroids \>2 mg/kg prednisone equivalent
* Bone marrow transplant patients
* Cancer patients undergoing chemotherapy within 3 months of inclusion
* Stays shorter than 24h in the ICU will be exlcuded
* Absence of informed written consent of the patient if they are fit, or absence of informed written consent of the relative/caregiver (for patients unable to understand the information and in the absence of a relative/caregiver, emergency inclusion is authorized)
* Decision to forego life-sustaining therapy
* Patient under guardianship or comparable legal status
* Cohort 3: vHAP or VAP :
* AIDS
* Patient on high-dose corticosteroids \>2 mg/kg prednisone equivalent
* Bone marrow transplant patients
* Cancer patients undergoing chemotherapy within 3 months of inclusion
* Absence of informed written consent of the patient if he is fit, or absence of informed written consent of the relative (for patients unable to understand the information and in the absence of a relative, emergency inclusion is authorized)
* Decision to forego life-sustaining therapy
* Patient under guardianship or comparable legal status
Primary outcome measure(s)
- To study the relationship between the composition of the respiratory microbiome at the start of treatment and time to response to antibiotic treatment. — 3 months
The measurement of interest for the primary endpoint will be the time to clinical success (resolution of symptoms) Clinical success is defined as : \- vHAP-VAP: resolution of the clinical symptoms that lead to the diagnosis on vHAP/VAP - To study the relationship between the composition of the respiratory microbiome at the start of treatment and time to response to antibiotic treatment. — 3 months
The measurement of interest for the primary endpoint will be the time to clinical success (resolution of symptoms) Clinical success is defined as : \- CAP: resolution of fever and dyspnea, or oxygen therapy requirement clinical symptoms - To study the relationship between the composition of the respiratory microbiome at the start of treatment and time to response to antibiotic treatment. — 3 months
The measurement of interest for the primary endpoint will be the time to clinical success (resolution of symptoms) without subsequent microbiological failure Microbiological failure is defined as: \- Persistence in standard culture of respiratory samples, of the microorganisms causing the pneumonia, independently from antibiotic susceptibility - To study the relationship between the composition of the respiratory microbiome at the start of treatment and time to response to antibiotic treatment. — 3 months
The measurement of interest for the primary endpoint will be the time to clinical success (resolution of symptoms) without subsequent microbiological failure OR Microbiological failure is defined as: Appearance, on respiratory sample, of a new pathogen considered as requiring a new antimicrobial therapy (superinfection) by the attending physician, before the test-of-cure visit (day 7-10). - To study the relationship between the composition of the respiratory microbiome at the start of treatment and time to response to antibiotic treatment. — 3 months
The measurement of interest for the primary endpoint will be the time to clinical success (resolution of symptoms) without subsequent microbiological failure or antibiotic resistance within the primary endpoint observation period, which will last 90 days after inclusion. Antibiotic resistance is defined as one of the 3 following definitions: \- Detection of the same pneumonia pathogen but with resistance to at least one of the given antibiotics, on any respiratory sample collected after initial diagnosis; - To study the relationship between the composition of the respiratory microbiome at the start of treatment and time to response to antibiotic treatment. — 3 months
The measurement of interest for the primary endpoint will be the time to clinical success (resolution of symptoms) without subsequent microbiological failure or antibiotic resistance within the primary endpoint observation period, which will last 90 days after inclusion. Antibiotic resistance is defined as one of the 3 following definitions: \- Occurrence of a new pathogen in respiratory specimens resistant to at least one of the given antibiotics; - To study the relationship between the composition of the respiratory microbiome at the start of treatment and time to response to antibiotic treatment. — 3 months
The measurement of interest for the primary endpoint will be the time to clinical success (resolution of symptoms) without subsequent microbiological failure or antibiotic resistance within the primary endpoint observation period, which will last 90 days after inclusion. Antibiotic resistance is defined as one of the 3 following definitions: \- Occurrence of a new pathogen in another site (infection, colonization or carriage) resistant the given antibiotic(s).
Trial sites (6)
| Facility | City | Region | Status |
|---|---|---|---|
| Hospital Beaujon | Clichy | France | Active Not Recruiting |
| CHU Nantes - Saint Herblain | Nantes | France | Not Yet Recruiting |
| CHU Nantes - Saint Herblain | Nantes | France | Not Yet Recruiting |
| CHU Nantes | Nantes | France | Active Not Recruiting |
| Hospital Bichat | Paris | France | Recruiting |
| Hospital Bichat | Paris | France | Active Not Recruiting |
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Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT06916481 on ClinicalTrials.gov ↗ ← All trials in France