Effectiveness of Antibiotic Therapy for Exacerbations of Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Situations That do Not Require Antibiotics for Acute Exacerbations of Mild-to-moderate Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: Amoxicillin and clavulanic acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo pills t.i.d. for 8 days | Drug: Placebo<br>* One pill to be taken every eight hours for 8 days<br>* Other names: It's placebo;|
| Active Comparator: Amoxycillin and clavulanic acid<br>Amoxycillin and clavulanate t.i.d. for 8 days | Drug: Amoxicillin and clavulanic acid<br>* 500-125 mg to be taken every eight hours for 8 days<br>* Other names: Augmentine 500-125 mg 24 pills;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Were Cured | Cure defined as the disappearance of the acute signs and symptoms related to the infection, with complete return to the previous situation of stability | Day 9-11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days Till the Next Exacerbation | 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. | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Antibiotics