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

Sponsor

University Hospital Muenster (Other)

Overall Status

Completed

CT.gov ID

NCT00669760

Collaborator

Mukoviszidose eV Bonn Germany (Other)

195

Enrollment

Locations

Duration (Months)

11.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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
1. 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	Phase
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 :

Jul 1, 2008

Actual Primary Completion Date :

Jul 1, 2011

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Observation CF-patients with persistent culture of Staphylococcus aureus in their respiratory specimens	Other: non-interventional study does not apply Other Names: does not apply

Arm

Intervention/Treatment

Observation

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

Other: non-interventional study

does not apply

Other Names:

does not apply

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

	Site	City	Country	Postal Code
1	Medizinische Universität Innsbruck	Innsbruck	Austria	6020
2	Charite Berlin Campus Benjamin Franklin	Berlin	Germany	12200
3	Clinic for Children and Adolescents Ruhr University Bochum St Josef Hospital	Bochum	Germany	44791
4	Universitätsklinikum Carl Gustav Carus	Dresden	Germany	01307
5	Heinrich-Heine University Duesseldorf	Duesseldorf	Germany	40225
6	University Clinics Essen	Essen	Germany	45122
7	Ruhrlandklinik Essen-Heidhausen	Essen	Germany	45239
8	Universitätsklinikum Halle	Halle	Germany	06120
9	Dres Heuer-Runge-Sextro	Hamburg	Germany	22763
10	Medical School Hannover	Hannover	Germany	30625
11	University Clinics Jena	Jena	Germany	07743
12	Children's Hospital Park Schoenfeld	Kassel	Germany	34121
13	Universitätsklinikum Leipzig	Leipzig	Germany	04103
14	University Clinics Muenster	Muenster	Germany	48149
15	Clemenshospital	Muenster	Germany	48153
16	Children's Hospital Osnabrueck	Osnabrueck	Germany	49082
17	University Clinics Tuebingen	Tuebingen	Germany	72076