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Azithromycin Treatment of Patients With Chronic Obstructive Pulmonary Disease (COPD) and Tracheostomy

Phase 2
Terminated
Conditions
COPD
Tracheostomy
Registration Number
NCT00323986
Lead Sponsor
University of Milan
Brief Summary

Aims of the study

* to evaluate the rate of enteric gram negative bacteria colonization in tracheotomised COPD patients

* to evaluate the effect of azithromycin long-term treatment on Pseudomonas aeruginosa colonization and colony counts, and on reduction of the number of exacerbations/hospitalisations, antibiotic courses and steroid use.

* to evaluate the Quality of Life of patients treated and not treated with azithromycin, using a validate Italian version of St George questionnaire

* to evaluate the rate of chronic colonization with atypical pathogens

* to evaluate the safety and tolerability of a long-term treatment with azithromycin, including a survey on possible bacterial antibiotic resistance pattern variations

Detailed Description

Methods. Study Design Prospective, randomised, multicentre study. Centers

* Dott. E. Guffanti, IRCCS INRCA Casatenovo, Varese Italy

* Prof. F. Blasi, Università degli Studi di Milano, IRCCS Ospedale Maggiore Milan Italy

* Dott, M. Confalonieri, Ospedale Trieste, Italy Patients

We plan to enrol 30 patients :

Inclusion criteria

* Age \> 45 years

* Tracheotomy

* History of COPD demonstrated by pulmonary function tests

* Informed Consent Exclusion criteria

* Allergy to macrolides

* Life expectancy \< 1 year

Exhaled breath condensate (EBC) The breath condensate samples is collected using a specially designed condensing chamber (Ecoscreen; Jaeger, Hoechberg, Germany). The exhaled air entered and left the chamber though one-way inlet and outlet valves, thus keeping the chamber closed. The subjects wear noseclips and breathed tidally through a mouthpiece connected to the condenser for ten minutes. Approximately 1 ml of the sampled material is transferred to 2-ml plastic tube and stored at -70°C.

Interleukin-6 assay Interleukin-6 concentrations in the breath condensate will be measured using a specific enzyme immunoassay kit (EIA) (Cayman Chemical, Ann Arbor, USA). The assay is directly validated by means of gas chromatography/mass spectrometry in order to obtain a high correlation (r=0.95) between known amounts of IL-6 and the concentration measured by the EIA. The detection limit of the assay was 1.5 pg/ml after a two-hour development period.

TNF alfa TNF-alfa serum levels will be measured by enzyme immunoassay (Cayman Chemical, Ann Arbor, USA)

Microbiology Quantitative culture of tracheal aspirate will be performed at steady state, every 3 months and at exacerbation. Molecular biology techniques for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Chlamydia pneumoniae and Mycoplasma pneumoniae identification will be also applied on the same specimens.

Timetable Enrolment: between January 2004 and December 2005 Visits : Every 3 months and on each exacerbation/hospitalization a visit will be performed. Every month a phone call will be performed.

Follow-up: 12 months. End of the study : July 2006

Visit

1. Visit 1. A complete history will be recorded. Inclusion and exclusion criteria will be checked. Informed consent will be collected and QoL questionnaire completed. Tracheal aspirate will be performed and divided into two aliquots : one for the local microbiology lab for quantitative cultures, and one for central lab for bacterial detection by PCR (stored at -80°C). Exhaled breath samples will be obtained.

2. Follow-up visits. Every 3 months the patients will be recalled at the center and all Visit 1 procedures will be repeated. Number of exacerbations/hospitalisation will be recorded and QoL questionnaire completed.

3. Exacerbation/hospitalisation visit. In presence of symptoms deterioration patients will be instructed to contact the center for a visit. All Visit 1 procedures will be repeated.

4. End of the study visit. At the end of the 12 month follow-up all Visit 1 procedures will be repeated. Number of exacerbations/hospitalisation will be recorded and QoL questionnaire completed.

Treatment Patients will be randomised to receive usual care or usual care + Azithromycin 500 mg o.d. three day-a-week (Monday, Tuesday, Wednesday) for 6 months.

Outcome measures

* reduction of inflammatory cytokines in EBC

* reduction of colony counts/eradication of bacteria on bronchial aspirates

* reduction of number of exacerbations/hospitalisations

* reduction of steroids and antibiotics use

* Quality of life

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
30
Inclusion Criteria
  • Age > 45 years Tracheotomy History of COPD demonstrated by pulmonary function tests Informed Consent
Exclusion Criteria
  • Allergy to macrolides Life expectancy < 1 year

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
reduction of number of exacerbations
reduction of number of hospitalisations
Secondary Outcome Measures
NameTimeMethod
reduction of colony counts/eradication of bacteria on bronchial aspirates
reduction of steroids and antibiotics use
reduction of inflammatory cytokines in EBC

Trial Locations

Locations (3)

Istituto Malattie Respiratorie University of Milan

🇮🇹

Milan, Italy

University Hospital Trieste

🇮🇹

Trieste, Italy

Istituto Nazionale di riposo e cura per anziani (INRCA)

🇮🇹

Casatenovo, Italy

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