Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Antibiotics
Brief summary
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
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.
Interventions
DRUGPlacebo
One pill to be taken every eight hours for 8 days
500-125 mg to be taken every eight hours for 8 days
Sponsors
Fondo de Investigacion Sanitaria
Societat Catalana de Medicina Familiar i Comunitària, Assoc. (CAMFiC)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Were Cured | Day 9-11 | Cure defined as the disappearance of the acute signs and symptoms related to the infection, with complete return to the previous situation of stability |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days Till the Next Exacerbation | One year | 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. |
Countries
Spain
Participant flow
Recruitment details
353 patients invited to participate in this trial, 32 did not fulfill the inclusion criteria (14 presented a forced expiratory volume in one second \[FEV1\]/forced vital capacity \[FVC\] ratio \> 70% and 18 a FEV1\<50%). Three more had a positive X-ray for pneumonia and were therefore excluded.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo pills t.i.d. for 8 days | 156 |
| Amoxycillin and Clavulanic Acid Amoxycillin and clavulanate t.i.d. for 8 days | 162 |
| Total | 318 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Amoxycillin and Clavulanic Acid | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 116 Participants | 102 Participants | 218 Participants |
| Age, Categorical Between 18 and 65 years | 46 Participants | 54 Participants | 100 Participants |
| Age Continuous | 68.4 years STANDARD_DEVIATION 9.9 | 67.8 years STANDARD_DEVIATION 11 | 68.1 years STANDARD_DEVIATION 10.4 |
| Region of Enrollment Spain | 162 participants | 156 participants | 318 participants |
| Sex: Female, Male Female | 27 Participants | 34 Participants | 61 Participants |
| Sex: Female, Male Male | 135 Participants | 122 Participants | 257 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 152 | 23 / 158 |
| serious Total, serious adverse events | 0 / 152 | 0 / 158 |
Outcome results
Primary
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
Time frame: Day 9-11
Population: Clinical cure at end of therapy visit at day 9-11 in the ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Patients Who Were Cured | 91 Participants |
| Amoxycillin and Clavulanic Acid | Number of Patients Who Were Cured | 117 Participants |
Comparison: For the comparison of the efficacy of antibiotic versus placebo, we accepted a null hypothesis if the cure rate in the intervention group was the same or ±7% as that observed in the placebo arm. Based on previous studies, the expected rate of cure among patients assigned to antibiotic therapy was 90%. For an alpha of 0.05 and a beta of 0.2 and accepting possible losses of 15%, we calculated that the sample size is 677 patients in total.p-value: <0.0595% CI: [3.7, 24.3]Chi-squared
Secondary
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.
Time frame: One year
Population: Patients with clinical success at the end of therapy visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Number of Days Till the Next Exacerbation | 233 Days |
| Amoxycillin and Clavulanic Acid | Number of Days Till the Next Exacerbation | 160 Days |