The purpose of this study is to determine the effectiveness of antibiotic therapy for patients with acute exacerbations of mild-to-moderate chronic obstructive pulmonary disease.

Antibiotics are usually prescribed for acute exacerbations of chronic obstructive pulmonary disease (COPD) even though their benefit in mild-to-moderate COPD is not demonstrated. The aim of this study is to assess the effectiveness of antibiotic therapy for exacerbations of COPD, what clinical variables are associated with an improved clinical response with antibiotic therapy with respect to placebo and to identify which patients might recover from an acute exacerbation without antibiotic therapy. Methodology: prospective, randomised, double blind, placebo-controlled clinical trial, in which exacerbations (at least one criterion present: increase of dyspnoea, increase of sputum production and/or increase of purulence) of patients older than 40 yr., smokers or ex-smokers of more than 10 pack-years, with COPD and FEV1 greater than 50%, diagnosed by spirometry and a predicted ratio FEV1/FVC<0.7%. Exclusion criteria: severe COPD (FEV1<50%), active neoplasm, tracheotomy, pneumonia, hospitalization criteria, patients previously being on antibiotics, immunodepressed, history of hypersensitivity to beta-lactams or intolerance to clavulanate, enrollment in other clinical trials, patients who refuse to take part in this study, and patients who have not had a spirometry test for the past two years. Sample size: 677 patients.

Interventions: first visit: the patient will be given details of the clinical trial and will be asked to sign informed consent; other data: sputum color, chest X-ray ordered to rule out pneumonia, C-reactive protein levels, and peak flow measurement. The patient will be randomised to receive amoxicillin plus clavulanate or placebo and will be scheduled to return for a 2nd follow-up visit after 3 or 4 days to assess the clinical response and peak flow measurements and to rule out any worsening of the condition. Third visit: scheduled after 9-11 days to assess the clinical response, drug-compliance and peak flow measurement. Fourth visit after 15-20 days for clinical assessment and to observe whether any relapses have occurred. Date of the following exacerbation will be recorded.

• Drug: Placebo
• Drug: Amoxicillin and clavulanic acid

• Placebo Comparator: Placebo pills t.i.d. for 8 days
• Active Comparator: Amoxycillin and clavulanate t.i.d. for 8 days

Inclusion Criteria:

• Acute exacerbations (at least one criterion present: increase of dyspnoea, increase of sputum production and/or increase of purulence) of
• patients older than 40 years old,
• smokers or ex-smokers of more than 10 pack-years,
• with COPD and FEV1 greater than 50%, diagnosed by spirometry and a predicted ratio FEV1/FVC<0.7%.

Exclusion Criteria:

• Severe COPD (FEV1<50%)
• Pneumonia
• Active neoplasm
• Tracheotomy
• Criteria for hospitalisation
• Patients previously being on antibiotics
• Immunodepressed patients
• History of hypersensitivity to beta-lactams or intolerance to clavulanate
• Enrollment in other clinical trials
• Patients who refuse to take part in this study
• Patients who have not had a spirometry test for the past two years