Dissection of Staphylococcus Aureus Infection From Colonization in Cystic Fibrosis Patients - Full Text View

Sponsor:	University Hospital Muenster
Collaborator:	Mukoviszidose eV Bonn Germany
Information provided by:	University Hospital Muenster
ClinicalTrials.gov Identifier:	NCT00669760

Purpose

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	Intervention
Cystic Fibrosis	Other: non-interventional study

Study Type:	Observational
Study Design:	Case-Only, Prospective
Official Title:	Dissection of Staphylococcus Aureus Infection From Colonization in Cystic Fibrosis Patients, a Non-Interventional, Prospective, Longitudinal Multicenter Study.

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

U.S. FDA Resources

Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:

bacterial load of sputum cultures [high (>/= 1000000CFU/ml); low (<1000000CFU/ml)] [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

antibody titres against S. aureus specific antigens; S100A12, IL-8, TNF-alpha, CRP [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Biospecimen Retention: None Retained

Biospecimen Description:

Estimated Enrollment:	248
Study Start Date:	July 2008
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Observation CF-patients with persistent culture of Staphylococcus aureus in their respiratory specimens	Other: non-interventional study does not apply

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

Ages Eligible for Study:	6 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00669760

Contacts

Contact: Barbara C Kahl, MD

49-251-835-5381

kahl@uni-muenster.de

Locations

Germany
University Clinics Muenster	Recruiting
Muenster, Germany, 48149
Contact: Angelika Duebbers, MD adue@uni-muenster.de
Principal Investigator: Angelika Duebbers, MD
University Clinics Essen	Recruiting
Essen, Germany, 45122
Contact: Uwe Mellies, MD 49-201-723-3355 Uwe.Mellies@uk-essen.de
Principal Investigator: Uwe Mellies, MD
Ruhrlandklinik Essen-Heidhausen	Recruiting
Essen, Germany, 45239
Contact: Helmut Teschler, MD 49-201-937-0 teschlerh@t-online.de
Principal Investigator: Helmut Teschler, MD
Heinrich-Heine University Duesseldorf	Not yet recruiting
Duesseldorf, Germany, 40225
Contact: Antje Schuster, MD 49-211-811-8297
Principal Investigator: Antje Schuster, MD
Medical School Hannover	Not yet recruiting
Hannover, Germany, 30625
Contact: Manfred Ballmann, MD 49-511-532-3220 Ballmann.Manfred@mh-hannover.de
Contact: Sibylle Junge, MD 49-511-532-3220 Junge.Sibylle@MH-Hannover.de
Principal Investigator: Manfred Ballmann, MD
Dr. Peter Kuester	Recruiting
Muenster, Germany, 48153
Contact: Peter Kuester, MD 49-251-976-2930 p.kuester@clemenshospital.de
Principal Investigator: Peter Kuester, MD
University Clinics Koeln	Not yet recruiting
Koeln, Germany, 50924
Contact: Ernst Rietschel, MD +49-221-4786172 ernst.rietschel@uk-koeln.de
Principal Investigator: Ernst Rietschel, MD
Children's Hospital Park Schoenfeld	Not yet recruiting
Kassel, Germany, 34121
Contact: Martin Schebek, MD martin.schebek@park-schoenfeld.de
Sub-Investigator: Martin Schebek, MD
Children's Hospital Osnabrueck	Recruiting
Osnabrueck, Germany, 49082
Contact: Ruediger Szczepanski, MD szczepanski@kinderhospital.de
Contact: Ruediger Szczepanski, MD szczepanski@kinderhospital.de
Sub-Investigator: Ruediger Szczepanski, MD
Charite Berlin Campus Benjamin Franklin	Not yet recruiting
Berlin, Germany, 12200
Contact: Doris Staab, MD +49-30-84454932 doris.staab@charite.de
Principal Investigator: Doris Staab, MD
University Clinics Tuebingen	Not yet recruiting
Tuebingen, Germany, 72076
Contact: Joachim Riethmueller, MD +49-7071-29 81391 joachim.riethmueller@uni-tuebingen.de
Principal Investigator: Joachim Riethmueller, MD
University Clinics Jena	Recruiting
Jena, Germany, 07743
Contact: Jochen Mainz, MD Jochen.Mainz@med.uni-jena.de
Sub-Investigator: Jochen Mainz, MD

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 This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Dept. of Med. Microbiology, University Clinics Muenster, Germany ( Dr. Barbara C. Kahl )
Study ID Numbers:	Muko e.V. S05/07
Study First Received:	April 28, 2008
Last Updated:	December 8, 2008
ClinicalTrials.gov Identifier:	NCT00669760 History of Changes
Health Authority:	Germany: Federal Ministry of Education and Research

Keywords provided by University Hospital Muenster:

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

Additional relevant MeSH terms:

Pathologic Processes
Digestive System Diseases
Genetic Diseases, Inborn
Respiratory Tract Diseases
Cystic Fibrosis

Fibrosis
Lung Diseases
Infant, Newborn, Diseases
Pancreatic Diseases
Infection

ClinicalTrials.gov processed this record on November 27, 2009