Bacterial and Human Biomarkers of Prognostic Value for Severe Legionnaire's Disease

Not Applicable

Recruiting

• Conditions: Legionella
• Interventions: Other: Skin biopsy for genetic analyze

• Registration Number: NCT03064737
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

Legionnaires' disease (LD) is a relatively common pneumonia in France (1200 cases/year), 98% of cases are hospitalized and 40% require intensive care unit (ICU) admission. Risk factors that may predispose to acquisition of LD are well known. Some studies suggest that genetic factor may also enhance susceptibility to LD.

The mortality rate remains high (10% to 33% in ICUs) despite improved diagnostic and therapeutic management of patients. Few prospective studies have assessed the factors associated with LD outcomes, particularly death, and most of them involved a limited number of patients.

In a multicentre cohort study, the investigators recently identified risk factors associated with higher mortality such as female sex, age, ICU stay, renal failure, corticosteroid treatment and enhanced pro-inflammatory status, as assessed by higher C-reactive protein level (PMID: 22005914). Other factors are suspected but their involvement has not been formally demonstrated including a high infectious bacterial load, particular virulence of Legionella strain, and an in vivo selection of mutants resistant to prescribed antibiotics. Disease progression is highly variable from one patient to another, and usually remains unpredictable. There are no objective criteria to predict the prognosis of these patients.

The clinical course of patients with LD remains difficult to predict because no predictive biomarkers have yet been characterized and the demonstration of the presence of mutants to antibiotics in vivo has never been done.

The main objective of the study is to correlate the L. pneumophila load (detected by PCR) to the clinical outcome of the LD infection. Clinical severity will measured by the SOFA score (Sepsis -Related Organ Failure Assessment) or the PELOD score (Pediatric Logistic Organ Dysfunction).

Secondary objectives are to identify new host and bacterial biomarkers associated with poor outcome of LD.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-09-02
• Study First Submitted QC: 2017-02-21
• Study First Posted: 2017-02-27
• Study Start: 2017-08-23
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-04
• Last Update Posted: 2022-05-05
• Primary Completion: 2024-01-31
• Study Completion: 2025-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Adult patients with medical and biological signs of legionnaires' disease.
• Pediatric patients regardless of age but with a minimum weight of 7.5 kg with medical and biological signs of legionnaires' disease.
• Patient and/or his/her legal representative have reviewed the patient information/informed consent form and have given written informed consent.

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Exclusion Criteria

• None Legionella pneumophila Legionnaires' disease.
• Patients for whom respiratory secretions can't be obtained.
• Cases diagnosed only by serology.
• Outpatients.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
This study is a non-drug one arm study	Skin biopsy for genetic analyze	Skin biopsy for genetic analyze

Primary Outcome Measures

Name	Time	Method
Legionnaire's disease severity measured by SOFA/PELOD score	At Hospital Output, on average 1 Day	No other specific timeframe could be provided, it will depend on patients' condition. The study will evaluate correlation between the L. pneumophila load (quantify by molecular method) to the clinical outcome of the LD infection
Bacterial load measured by PCR	At Hospital Output, on average 1 Day	No other specific timeframe could be provided, it will depend on patients' condition. The study will evaluate correlation between the L. pneumophila load (quantify by molecular method) to the clinical outcome of the LD infection

Secondary Outcome Measures

Name	Time	Method
Pulmonary microbiota	At inclusion, up to 48 hours	Metagenomic approaches and NGS will be used to associate a specific microbiota, or changes in the severity of LD infection
Genomic analyzes	At inclusion, up to 48 hours	Genomic analyzes of bacterial genes will be associated with the legionella severity
Specific cytokine profile	Up to Day 5	Cytokine profile will be measured at local level (pulmonary) and/ or systemic level (serum) and associated with severity

Trial Locations

Locations (18)

CHU Amiens; 🇫🇷 Amiens, France

CHU d'Angouleme; 🇫🇷 Angoulême, France

Hôpital Saint Louis - APHP; 🇫🇷 Paris, France

CHU Brest; 🇫🇷 Brest, France

Hôpital de la Croix Rousse; 🇫🇷 Lyon, France

CHU Saint Etienne; 🇫🇷 Saint-Étienne, France

CHU Grenoble; 🇫🇷 Grenoble, France

CHRU Besancon; 🇫🇷 Besançon, France

CHU Dijon; 🇫🇷 Dijon, France

Hôpital Tenon; 🇫🇷 Paris, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Hopital Edouard Heriot; 🇫🇷 Lyon, France

CHU Lille; 🇫🇷 Lille, France

CHU de Nantes; 🇫🇷 Nantes, France

CHU Rennes; 🇫🇷 Rennes, France

APHP Hôpital Bichat; 🇫🇷 Paris, France

CHU Strasbourg Nouvel Hôpital Civil; 🇫🇷 Strasbourg, France

CH Gustave Dron; 🇫🇷 Tourcoing, France