Identificador: TDX:1022
Autors: Moragas Moreno, Ana
Resum:
Background. Chronic obstructive pulmonary disease (COPD) constitutes one of the principal demands on healthcare in primary care. Acute exacerbations of COPD are typical events that characterize the course of the disease. Antimicrobial therapy remains a controversial issue, mainly in acute exacerbations of mild-to-moderate COPD. Even though most of the patients attended in the community correspond to mild and moderate COPD, antibiotics are highly prescribed for exacerbations in Spain. Aims. The main objective was to evaluate the effectiveness of antibiotic therapy compared with placebo at day 9-11 in acute exacerbations of mild-to-moderate COPD. The secondary objectives were to evaluate the rate of clinical success of antibiotic therapy compared with placebo at day 20 and assess the symptom-free interval, i.e. days till next exacerbation in both groups. Design. Multicentre, parallel, double-blinded placebo-controlled randomized clinical trial carried out from January 2006 to June 2011. Study setting: Twenty-three primary care centres in Catalonia. Subjects. Patients aged 40 or older, smokers or ex-smokers of ten packs-year or more, with spirometrically-based diagnosis of mild-to-moderate COPD (forced expiratory volume in one second (FEV1) > 50% expected and FEV1/forced vital capacity ratio < 0.7% expected) from a lung function test performed within 24 months prior to inclusion, and the presence of an acute exacerbation defined as the presence of at least one of the following signs and symptoms: increase of dyspnoea, increase in sputum volume and/or increase of sputum purulence. Patients with bronchial asthma, hypersensitivity to β-lactams, bronchiectasis of origin other than COPD, active neoplasm, tracheotomy, presence of radiological signs of pneumonia or hospital admission criteria, and those who refused to participate in the study were all excluded. Measurements and interventions. The patients were randomised into two treatment groups: amoxicillin and clavulanic acid (500/125 mg three times daily for 8 days) or placebo three times daily for 8 days). The use of antithermics or analgesics was allowed as were short-acting and long-acting β-adrenergics, anticholinergics, ii | P a g e theophyllines, inhaled or oral corticosteroids and any medication that the patient may been have taken for chronic disease and which had been initiated three months prior to inclusion in the study, except for antibiotics. Cure was defined as the disappearance of the acute signs and symptoms related to the infection, improvement, as the non-complete resolution of the symptoms and failure was defined as with an insufficient reduction in the signs and symptoms of infection. Clinical success was considered when either cure or improvement was observed. Results. A total of 353 subjects were included in the study. Forty-three patients were excluded as they did not fulfil the inclusion criteria. Three hundred ten (158 patients in the amoxicillin and clavulanic acid arm and 152 patients in the placebo arm) fulfilled all the criteria for efficacy analysis. The mean age was 68.1 years (SD: 10.4 years) and the mean FEV1 was 65% (SD: 11.9%). No differences were found between the two groups regarding the different basal variables analysed. A total of 117 patients assigned to the intervention group (74.1%) and 91 to control group (59.9%) were considered cured at days 9-11 (p<0.05). In the multivariate regression analysis failure was associated with C-reactive protein (CRP) concentrations ≥ 40 mg/l (OR: 7.9; 95% CI: 3.9 –16.3), placebo treatment (OR: 2.9; 95% CI: 1.4 – 6) and presence of coronary heart disease (OR: 2.6; 95%CI: 1 – 6.7). Among patients treated with placebo clinical predictors for failure were CRP ≥ 40 mg/l (OR of cure: 0.1; 95% CI: 0 – 0.2) and purulent sputum (OR: 0.2; 95% CI: 0 – 0.7). The predictive value of Anthonisen criteria for clinical outcome in those patients was 0.708 (95% CI: 0.616 – 0.801) and rose to 0.842 (95% CI: 0.76 – 0.924; p<0.001) when CRP ≥ 40 mg/l was added. Regardless of the number the Anthonisen criteria, the presence of both CRP low levels and uncoloured sputum was associated with a clinical success of 90% among patients not treated with antibiotics. Conclusions. Treatment of acute exacerbations of mild-to-moderate COPD with amoxicillin and clavulanic acid is more effective than placebo. Nonetheless, this thesis indicates when antibiotic therapy may be safely withheld in acute exacerbations of mild-to-moderate COPD. Key words. Acute exacerbations. Mild-to-moderate COPD. Antibiotic. Effectiveness.Randomised clinical trial.
Repositori URV