To assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year can decrease the exacerbation rate in the year of treatment.
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Reduction in the number of exacerbations in the year of treatment.
Secondary outcome
- Measurement of lungfunction parameters: FEV1 (L), FVC (L), IC(L), 6 minute
walking test.
- BODE-index.
- Disease specific quality of life measured by St. George*s Respiratory
Questionnaire (SGRQ).
- Generic health status measured by the 12-Item Short Form Health Survey
(SF-12).
- Assessment of presence of type D personality by DS-14 questionnaire.
- Indication of anxiety and depression by Hospital Anxiety Depression Scale
(HADS).
- Microbiology: Sputum specimens will be cultured. Polymerase chain reaction
(PCR) in sputum and serology in serum for atypical and viral microorganisms
will be performed. A rectal swab will be performed to to assess the effect of
maintenance antibiotics on the intestinal flora via ISpro. Faeces samples will
be collected to assess and characterize antibiotic resistancy patterns via
metagenomic sequencing. When sputum is not obtained, a throat swab will be
performed.
- Measurement of inflammatory markers in serum.
- Difference in treatment effect between subjects with and without steroid
maintenance therapy as hypothesis-generating secondary analysis.
- Decrease in percentage of clinical versus outpatient department exacerbations.
- Adverse events of treatment.
- Length of hospital stay.
- Time till next exacerbation.
Background summary
Chronic obstructive pulmonary disease (COPD) is characterized by progressive
development of airflow limitation that is poorly reversible. Because of a poor
understanding of COPD pathogenesis, treatment is mostly symptomatic and new
therapeutic strategies are limited. There is a direct relationship between the
severity of the disease and the intensity of the inflammatory response. One of
the hypothesis for persistent airway inflammation, besides smoking, is that the
presence of recurrent infections is responsible for this condition. Macrolide
antibiotics have a bacteriostatic as well as anti-inflammatory properties.
There is consistent evidence that macrolide therapy reduces infective
exacerbations, decreases the requirement for additional antibiotics and
improves nutritional measures in patients with cystic fibrosis, which is also a
chronic inflammatory pulmonary disease. Until now, the number of studies
investigating macrolide therapy in COPD is clearly extremely limited, but the
positive benefit seen in other chronic inflammatory pulmonary diseases suggests
that macrolide therapy can also have beneficial effects in patients with COPD.
Study objective
To assess whether maintenance treatment with macrolide antibiotics in COPD
patients with three or more exacerbations in the previous year can decrease the
exacerbation rate in the year of treatment.
Study design
The study will be conducted as a prospective randomized double-blind
placebo-controlled trial.
Intervention
Subjects will be randomized to receive either Azithromycin 500mg 3 times a week
or placebo 3 times a week.
Study burden and risks
The study participants will come to the outpatient department 5 times in 1
year. During all 5 visits a few questionnaires will be taken, blood and sputum
samples will be taken, a lung function test and a 6 minute walking test will be
done. Each of these visits will take about 1,5 to 2 hours.
Also the study participants will have to take either azithromycin or placebo 3
times a week during 1 year.
The burden of the tests is not very high. The tests are standard test which
take place daily. For the rectal swabs and faeces samples the study
participants have to give additional consent as these are not routine tests.
The risks for the study subjects are explained in the patient information
folder.
Postbus 90158
4800 RK Breda
NL
Postbus 90158
4800 RK Breda
NL
Listed location countries
Age
Inclusion criteria
COPD patients who have had 3 or more exacerbations in the previous year, which have been treated with antibiotics and/or corticosteroids.
Exclusion criteria
Use of antibiotics or a course of high doses of systemic steroids defined as more than 10 mg of prednisone a day within a month prior to involvement in the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-015857-19-NL |
| ClinicalTrials.gov | NCT00985244 |
| CCMO | NL29500.101.09 |