Defining long-term macrolide maintenance therapy in COPD: a single center randomized controlled trial:

Chronic obstructive pulmonary disease (COPD) is characterized by small airway
disease and parenchymal destruction. Acute exacerbations of COPD (increased
cough, dyspnoea and/or increased sputum) are associated with increase mortality
and worsening of COPD and/or level of health. Inhalation therapy with long
acting antimuscarinic agents (LAMA), long acting β agonists (LABA) and inhaled
corticosteroid-LABA combination inhalers significantly reduces AECOPD.
Nonetheless a selection of patients still experience frequent exacerbation. In
this group The Columbus study showed that macrolide maintenance therapy
resulted in a decreased exacerbation frequency . However, macrolide resistance
and adverse effects are of great concern.
The duration of macrolide maintenance therapy has not been studied yet. Studies
were performed with a follow up period of a maximum period of one year. There
is no information available about the value of azithromycin maintenance
treatment for more than one year.

The primary objectives of this study are:
· To assess the time to first exacerbation of COPD, measured from the time of
randomization


The secondary objectives of this study are:
· To evaluate the improvement of quality of life by Saint George*s Respiratory
Questionnaire;
· To evaluate pulmonary function (FEV1)
· To evaluate the frequency of exacerbation requiring an intervention with
systemic corticosteroids and antibiotics (oral/intravenous [i.v.]) in subjects
with COPD.
· To assess the microbiology of sputum production
· To assess the safety and tolerability of long term azithromycin

Further objectives include:
· To assess the inflammatory response measured by the following inflammatory
markers: high-sensitivity C-reactive protein, the erythrocyte sedimentation
rate, polymorphonuclear leukocytes, neutrophils; eosinophils; interleukin-6,
interleukin-8, and myeloperoxidase;

Double blind randomized placebo controlled single center trial

Randomizing in either continuation of macrolide maintenance therapy or
withdrawal of maintenance therapy

Randomizing into the placebo group could hypothetically mean that exacerbation
is increasing, but we consider this chance extremely low.The blood test can
cause local pain and bruising.The lung function test and the 6-minute walk test
are without danger, there may be some fatigue. Sputum culture / throat culture,
no known risks