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

Sponsor

University of Milan (Other)

Overall Status

Terminated

CT.gov ID

NCT00323986

Collaborator

Pfizer (Industry)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
COPD Tracheostomy	Drug: azithromycin (drug)	Phase 2

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

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.
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.
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.
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

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Azithromycin Treatment of Patients With Chronic Obstructive Pulmonary Disease (COPD) and Tracheostomy. Effects on Recurrent Respiratory Infections, Inflammatory Parameters and Bacterial Persistence

Study Start Date :

Oct 1, 2004

Study Completion Date :

Apr 1, 2006

Outcome Measures

Primary Outcome Measures

reduction of number of exacerbations []
reduction of number of hospitalisations []

Secondary Outcome Measures

reduction of colony counts/eradication of bacteria on bronchial aspirates []
reduction of steroids and antibiotics use []
reduction of inflammatory cytokines in EBC []

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Istituto Nazionale di riposo e cura per anziani (INRCA)	Casatenovo	Italy	23880
2	Istituto Malattie Respiratorie University of Milan	Milan	Italy	20122
3	University Hospital Trieste	Trieste	Italy	34100