Effectiveness of Antibiotic Therapy for Exacerbations of Chronic Obstructive Pulmonary Disease (TRANCE)

• Number of Patients Who Were Cured [ Time Frame: Day 9-11 ] [ Designated as safety issue: Yes ]
  Cure defined as the disappearance of the acute signs and symptoms related to the infection, with complete return to the previous situation of stability
  
  

• Number of Days Till the Next Exacerbation [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  For the assessment of the time till next exacerbation patients were monitored over a period of 365 days on a three-monthly basis. Patients were instructed to contact their physician immediately if there was any change in their health status. Diagnosis of a new exacerbation was based on the same clinical criteria described previously. For the calculation of time to the next exacerbation, all clinical failures occurring during therapy were counted as zero exacerbation-free interval days.
  
  

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.