Dissection of Staphylococcus Aureus Infection From Colonization in Cystic Fibrosis Patients

NCT ID: NCT00669760

Last Updated: 2015-01-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 195 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2015-01-31

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

Conditions

Cystic Fibrosis

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Observation

CF-patients with persistent culture of Staphylococcus aureus in their respiratory specimens

non-interventional study

Intervention Type: OTHER

does not apply

Interventions

non-interventional study

does not apply

Intervention Type: OTHER

Other Intervention Names

does not apply

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

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Mukoviszidose eV Bonn Germany

UNKNOWN

Sponsor Role: collaborator

University Hospital Muenster

OTHER

Sponsor Role: lead

Responsible Party

Barbara Kahl

Prof. Dr. Barbara Kahl

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Barbara C Kahl, MD

Role: PRINCIPAL_INVESTIGATOR

Dept. Med. Microbiology, University Clinics Muenster, Germany

Locations

Medizinische Universität Innsbruck

Innsbruck, , Austria

Charite Berlin Campus Benjamin Franklin

Berlin, , Germany

Clinic for Children and Adolescents Ruhr University Bochum St Josef Hospital

Bochum, , Germany

Universitätsklinikum Carl Gustav Carus

Dresden, , Germany

Heinrich-Heine University Duesseldorf

Düsseldorf, , Germany

University Clinics Essen

Essen, , Germany

Ruhrlandklinik Essen-Heidhausen

Essen, , Germany

Universitätsklinikum Halle

Halle, , Germany

Dres Heuer-Runge-Sextro

Hamburg, , Germany

Medical School Hannover

Hanover, , Germany

University Clinics Jena

Jena, , Germany

Children's Hospital Park Schoenfeld

Kassel, , Germany

Universitätsklinikum Leipzig

Leipzig, , Germany

University Clinics Muenster

Münster, , Germany

Clemenshospital

Münster, , Germany

Children's Hospital Osnabrueck

Osnabrück, , Germany

University Clinics Tuebingen

Tübingen, , Germany

Countries

Austria; Germany

References

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.

Reference Type: DERIVED

PMID: 27861524 (View on PubMed)

Other Identifiers

Muko e.V. S05/07

Identifier Type: -

Identifier Source: org_study_id