Oxidative stress contributes to
chronic obstructive pulmonary disease (
COPD) exacerbations and
antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal
Erdosteine in
COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for
Chronic Obstructive Lung Disease stage II/III. Patients received
erdosteine 300 mg twice daily or placebo added to usual
COPD therapy for 12 months. The primary outcome was the number of acute exacerbations during the study.In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted)
erdosteine reduced the exacerbation rate by 19.4% (0.91 versus 1.13 exacerbations·patient-1·year-1 for
erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient-1·year-1 for
erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient-1·year-1 for
erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group.
Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for
erdosteine and placebo, respectively; p=0.023).
Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.In patients with
COPD,
erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and
erdosteine treatment groups.