A strategy of bacterial eradication to prevent exacerbations of COPD in the frequent exacerbator phenotype population (GOAL study), a prospective randomized controlled pilot study

Chronic obstructive pulmonary disease (COPD) is frequently aggravated by
exacerbations (AECOPD)*short periods (at least 48 h) of increased cough,
dyspnoea, and production of sputum. Exacerbations have a negative effect on
disease prognosis. Therefore, a primary goal of treatment is to reduce the
number of exacerbations. Until now long acting antimuscarinic agents (LAMAs),
long acting * agonists (LABAs) and inhaled corticosteroid-LABA combination
inhalers significantly reduced AECOPD. However, some patients remain
experiencing 2 or more AECOPD (frequent exacerbator phenotype). Three
prospective randomised double-blind studies showed that maintenance treatment
with macrolides significantly decreased exacerbation rate. However, the
development of macrolide resistance related to this treatment is a major
concern. Therefore, alternative strategies should be developed, which could
prevent AECOPD.
One of these strategies could be directed at eradicating the bacterial
causative agent of an exacerbation. It has been shown that in patients admitted
to hospital for AECOPD, bacterial infections were detected in 54.7 % of cases
and, more importantly, that the exacerbations were more severe than those in
patients with non-infectious causes. It has also been demonstrated that
patients with a positive sputum culture suffered more exacerbations per year
than did patients with the same degree of lung function impairment but without
a positive bacterial sputum culture. These findings emphasize the importance of
intensive antibiotic treatment able to eradicate bacteria that causes the
exacerbation, preventing further exacerbations.
Studies in Cystic fibrosis have shown, that intensive antibiotic therapy aimed
at eradication of Pseudomonas aeruginosa was effective in preventing and
delaying the onset of chronic infection.
In this study we hypothesize that an antibiotic treatment strategy consisting
of 14 days of oral antibiotics during a bacterial AECOPD combined with 28 days
of inhaled Levofloxacin could result in a delayed onset of a new exacerbation.
A bacterial exacerbation will be defined by the presence of an increased
Procalcitonin (PCT) value >0.25 µg/L or CRP value > 50 mg/L.

Investigation of the impact of a treatment consisting of inhalation antibiotics
and prolonged oral antibiotic course during a bacterial exacerbation on the
prevention of further exacerbations.

A prospective randomized controlled, open label, single center trial

These patients will be randomized into:
1.Treatment with Levofloxacin inhalation twice daily 240 mg for 28 days
administered via PARI LC PLUS jet nebuliser and oral antibiotics during 7 days
Or
2.Standard treatment with 7 days of oral antibiotics

Added to the standard care for patients admitted with an AECOPD

A number of pulmonary adverse events such as coughing and bronchospasm can
occur with outpatient use of aerosolized antibiotics. Benefit: possible
reduction in exacerbations and admissions because of an AECOPD, improvement of
other important clinical outcome parameters and improved eradication of
microorganisms.