Clinical trial NCT03064737: Bacterial and Human Biomarkers of Prognostic Value for Severe Legionnaire's Disease
Official title: Bacterial and Human Biomarkers of Prognostic Value for Severe Legionnaire's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Legionella
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2017-02-27
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Legionnaire's disease severity measured by SOFA/PELOD score
timeFrame: At Hospital Output, on average 1 Day
measure: Bacterial load measured by PCR
timeFrame: At Hospital Output, on average 1 Day
Secondary outcomes:
measure: Specific cytokine profile
timeFrame: Up to Day 5
measure: Genomic analyzes
timeFrame: At inclusion, up to 48 hours
measure: Pulmonary microbiota
timeFrame: At inclusion, up to 48 hours
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Angoulême
country: France
facility: CHU d'Angouleme
city: Besançon
country: France
facility: CHRU Besancon
city: Brest
country: France
facility: CHU Brest
city: Dijon
country: France
facility: CHU Dijon
city: Dijon
country: France
facility: CHU Dijon
city: Grenoble
country: France
facility: CHU Grenoble
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: Hopital Edouard Heriot
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hôpital Saint Louis - APHP
city: Paris
country: France
facility: Hôpital Tenon
city: Paris
country: France
facility: APHP Hôpital Bichat
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rennes
country: France
facility: CHU Rennes
city: Saint-Étienne
country: France
facility: CHU Saint Etienne
city: Strasbourg
country: France
facility: CHU Strasbourg Nouvel Hôpital Civil
city: Tourcoing
country: France
facility: CH Gustave Dron
Study officials:
affiliation: Hospices Civils of Lyon
name: Gérard LINA
role: STUDY_CHAIR
References: