Clinical trial NCT00669760: Dissection of Staphylococcus Aureus Infection From Colonization in Cystic Fibrosis Patients
Official title: Dissection of Staphylococcus Aureus Infection From Colonization in Cystic Fibrosis Patients, a Non-interventional, Prospective, Longitudinal Multicenter Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
Staphylococcus aureus
persistent colonization-infection
clinical status
lung function
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Mukoviszidose eV Bonn Germany
First posted: 2008-04-30
Enrollment: 195
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: CF-patients with persistent S. aureus culture in their airway specimens

Brief summary: Staphylococcus aureus is not only one of the first pathogens infecting the airways of cystic fibrosis (CF) patients, but also a highly prevalent microorganism (\>60% of all CF patients; European and American CF registries; (4,25), which often persists for several years in the respiratory tract of CF patients.

The purpose of this study is to dissect infection by S. aureus from colonization. Therefore, the following non-interventional prospective, longitudinal multicenter study will be conducted to develop the following hypothesis:

CF patients with high bacterial loads are more likely to be infected by S. aureus than patients with low bacterial loads.

Primary endpoint: bacterial load of sputum cultures

Secondary endpoints:

* nasal carriage
* molecular analysis of S. aureus (Monoclonal/polyclonal)
* serum: S. aureus-specific antibodies, S100A12, IL-8, TNF-alpha
* sputum: S100A12, IL-8, myeloperoxidase
* S. aureus therapy regimens
* lung function tests: FEV1, deltaFVC , deltaMEF25
* BMI development

Inclusion criteria: S. aureus cultures for more than 6 months within the last year, children (\>6 years) and patients, who are able to perform lung function tests Exclusion criteria: P. aeruginosa and/or B. cepacia cultures from the specimens for more than 6 months within the last year before recruitment or during the study period In addition to microbiological investigations and clinical laboratory tests, the actual clinical situation will be evaluated and reported during the study period. The results of this observational study will be used to carefully plan a clinical interventional study. Furthermore, with the results it might be possible to characterize a subpopulation of patients, which is at greater risk for S. aureus infections.

Detailed description: Protocol synopsis Title: Dissection of Staphylococcus aureus infection from colonization in cystic fibrosis patients. A non-interventional prospective, 2-year longitudinal multicenter study

Study objectives: The aim of the study is to dissect S. aureus infection from colonization of the pathogen in airway secretions of CF patients during a 2 year period by means of a non-interventional, prospective, longitudinal multicenter study.

The following hypothesis will be developed:

CF patients with high bacterial loads are more likely to be infected by S. aureus than patients with low bacterial loads.

Definition of infection:

* change in volume, colour or consistency of sputum (exacerbation)
* increased cough
* malaise, fatigue or lethargy
* body temperature more than 38°C
* new or increased hemoptysis
* anorexia or weight loss
* sinus pain or tenderness
* change in sinus discharge
* change in chest sounds
* ten percent decrease in pulmonary function from a previous recorded value (FEV1, MEF25)
* radiographic changes indicative of pulmonary infection

Primary endpoint: bacterial load of sputum cultures \[high (\>/= 106CFU/ml); low (\<106CFU/ml)\]

Secondary endpoints are:

* assessment of nasal S. aureus carriage
* serum samples: antibody titres against S. aureus specific antigens; S100A12, IL-8,TNF-alpha, CRP
* molecular analysis of S. aureus colonization/infection (monoclonal or heteroclonal)
* sputa analysis: activity of S100A12, IL-8 and myeloperoxidase
* antibiotic treatment regimens against S. aureus
* body mass index
* lung function tests: FEV1, deltaFVC, deltaMEF25

Extensive microbiological investigations will be performed when the patients are seen at their regular visits in the outpatient clinics or if exacerbations occur. During the study period of 2 years, at least 8 visits to the outpatient clinic should be recorded. The following clinical parameters will be documented:

* lung function
* body mass index (weight/height)
* antibiotic treatment Diagnosis: CF and positive S. aureus cultures for more than 6 months within the last year Localisation of the study: multicenter study in Germany Number of centers: Seven centres agreed already to participate in the study. More centers have been and will be contacted.

Design: non-interventional prospective, longitudinal multicenter study Planned number of patients/volunteers: 228 Inclusion criteria: positive S. aureus cultures for more than 6 months within the last year; children (\>6 years) and patients with CF, who are able to perform lung function tests Exclusion criteria: Pseudomonas aeruginosa and/or Burkholderia cepacia colonization or infection for more than 6 months within the last year before recruitment; patients who have not been colonized with these pathogens before but acquire them within the study period and are colonized/infected for more than 6 months during the observation period

Eligibility criteria: Inclusion Criteria:

* positive S. aureus cultures for more than 6 months within the last year; children (\>6 years) and patients with CF, who are able to perform lung function tests

Exclusion Criteria:

* Pseudomonas aeruginosa and/or Burkholderia cepacia colonization or infection for more than 6 months within the last year before recruitment; patients who have not been colonized with these pathogens before but acquire them within the study period and are colonized/infected for more than 6 months during the observation period

Primary outcomes:
measure: bacterial load of sputum cultures [high (>/= 1000000CFU/ml); low (<1000000CFU/ml)]
timeFrame: 2 years
Secondary outcomes:
measure: antibody titres against S. aureus specific antigens; S100A12, IL-8, TNF-alpha, CRP
timeFrame: 2 years
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Berlin
country: Germany
facility: Charite Berlin Campus Benjamin Franklin
city: Bochum
country: Germany
facility: Clinic for Children and Adolescents Ruhr University Bochum St Josef Hospital
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: Heinrich-Heine University Duesseldorf
city: Essen
country: Germany
facility: University Clinics Essen
city: Essen
country: Germany
facility: Ruhrlandklinik Essen-Heidhausen
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Hamburg
country: Germany
facility: Dres Heuer-Runge-Sextro
city: Hannover
country: Germany
facility: Medical School Hannover
city: Jena
country: Germany
facility: University Clinics Jena
city: Kassel
country: Germany
facility: Children's Hospital Park Schoenfeld
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Muenster
country: Germany
facility: University Clinics Muenster
city: Muenster
country: Germany
facility: Clemenshospital
city: Osnabrueck
country: Germany
facility: Children's Hospital Osnabrueck
city: Tuebingen
country: Germany
facility: University Clinics Tuebingen
Study officials:
affiliation: Dept. Med. Microbiology, University Clinics Muenster, Germany
name: Barbara C Kahl, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Junge S, Gorlich D, den Reijer M, Wiedemann B, Tummler B, Ellemunter H, Dubbers A, Kuster P, Ballmann M, Koerner-Rettberg C, Grosse-Onnebrink J, Heuer E, Sextro W, Mainz JG, Hammermann J, Riethmuller J, Graepler-Mainka U, Staab D, Wollschlager B, Szczepanski R, Schuster A, Tegtmeyer FK, Sutharsan S, Wald A, Nofer JR, van Wamel W, Becker K, Peters G, Kahl BC. Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent Staphylococcus aureus. PLoS One. 2016 Nov 18;11(11):e0166220. doi: 10.1371/journal.pone.0166220. eCollection 2016.