Dissection of Staphylococcus Aureus Infection From Colonization in Cystic Fibrosis Patients (StaphCI)

• ClinicalTrials.gov Identifier: NCT00669760
• Recruitment Status: Completed
• First Posted: April 30, 2008
• Last Update Posted: January 7, 2015
• Sponsor: University Hospital Muenster
• Collaborator: Mukoviszidose eV Bonn Germany
• Information provided by (Responsible Party): Barbara Kahl, University Hospital Muenster

Study Description

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.

Condition or disease	Intervention/treatment
Cystic Fibrosis	Other: non-interventional study

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

Study Design

• Study Type: Observational
• Actual Enrollment: 195 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Dissection of Staphylococcus Aureus Infection From Colonization in Cystic Fibrosis Patients, a Non-interventional, Prospective, Longitudinal Multicenter Study.
• Study Start Date: July 2008
• Actual Primary Completion Date: July 2011
• Actual Study Completion Date: January 2015

Groups and Cohorts

Group/Cohort	Intervention/treatment
Observation; CF-patients with persistent culture of Staphylococcus aureus in their respiratory specimens	Other: non-interventional study; does not apply; Other Name: does not apply

Outcome Measures

Primary Outcome Measures :

1. bacterial load of sputum cultures [high (>/= 1000000CFU/ml); low (<1000000CFU/ml)] [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. antibody titres against S. aureus specific antigens; S100A12, IL-8, TNF-alpha, CRP [ Time Frame: 2 years ]

Biospecimen Retention:   None Retained

Sera

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

CF-patients with persistent S. aureus culture in their airway specimens

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

Contacts and Locations

Locations

Austria

Medizinische Universität Innsbruck

Innsbruck, Austria, 6020

Germany

Charite Berlin Campus Benjamin Franklin

Berlin, Germany, 12200

Clinic for Children and Adolescents Ruhr University Bochum St Josef Hospital

Bochum, Germany, 44791

Universitätsklinikum Carl Gustav Carus

Dresden, Germany, 01307

Heinrich-Heine University Duesseldorf

Duesseldorf, Germany, 40225

University Clinics Essen

Essen, Germany, 45122

Ruhrlandklinik Essen-Heidhausen

Essen, Germany, 45239

Universitätsklinikum Halle

Halle, Germany, 06120

Dres Heuer-Runge-Sextro

Hamburg, Germany, 22763

Medical School Hannover

Hannover, Germany, 30625

University Clinics Jena

Jena, Germany, 07743

Children's Hospital Park Schoenfeld

Kassel, Germany, 34121

Universitätsklinikum Leipzig

Leipzig, Germany, 04103

University Clinics Muenster

Muenster, Germany, 48149

Clemenshospital

Muenster, Germany, 48153

Children's Hospital Osnabrueck

Osnabrueck, Germany, 49082

University Clinics Tuebingen

Tuebingen, Germany, 72076

Sponsors and Collaborators

University Hospital Muenster

Mukoviszidose eV Bonn Germany

Investigators

• Principal Investigator: Barbara C Kahl, MD; Dept. Med. Microbiology, University Clinics Muenster, Germany

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Junge S, Görlich D, den Reijer M, Wiedemann B, Tümmler B, Ellemunter H, Dübbers A, Küster P, Ballmann M, Koerner-Rettberg C, Große-Onnebrink J, Heuer E, Sextro W, Mainz JG, Hammermann J, Riethmüller J, Graepler-Mainka U, Staab D, Wollschläger 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.

• Responsible Party: Barbara Kahl, Prof. Dr. Barbara Kahl, University Hospital Muenster
• ClinicalTrials.gov Identifier: NCT00669760
• Other Study ID Numbers: Muko e.V. S05/07
• First Posted: April 30, 2008
• Last Update Posted: January 7, 2015
• Last Verified: January 2015

Keywords provided by Barbara Kahl, University Hospital Muenster:

cystic fibrosis; Staphylococcus aureus; persistent colonization-infection; clinical status; lung function

Additional relevant MeSH terms:

Infection; Staphylococcal Infections; Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Gram-Positive Bacterial Infections; Bacterial Infections