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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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

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

Detailed Summary:
Sponsor: Hospices Civils de Lyon

Current Primary Outcome:

• Legionnaire's disease severity measured by SOFA/PELOD score [ Time Frame: 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 [ Time Frame: 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

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Specific cytokine profile [ Time Frame: Up to Day 5 ]
  Cytokine profile will be measured at local level (pulmonary) and/ or systemic level (serum) and associated with severity
• Genomic analyzes [ Time Frame: At inclusion, up to 48 hours ]
  Genomic analyzes of bacterial genes will be associated with the legionella severity
• Pulmonary microbiota [ Time Frame: 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

Original Secondary Outcome: Same as current

Information By: Hospices Civils de Lyon

Dates:
Date Received: September 2, 2016
Date Started: March 2017
Date Completion: November 2019
Last Updated: February 21, 2017
Last Verified: February 2017