Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine)

Inflammation and oxidative stress are involved in Chronic Obstructive Pulmonary Disease (COPD) exacerbations. Erdosteine is a muco-active agent with antioxidant, anti-inflammatory and bacterial anti-adhesive properties. Aim: To assess the efficacy of erdosteine added to usual maintenance therapy in reducing the frequency and duration of exacerbations. Methods: RESTORE is a randomized, double-blind, placebo-controlled, parallel group trial on 467 adult patients (40–80 years, 74% males; mean 64.8 years) with GOLD stage II-III COPD who were randomized to either erdosteine 300 mg bid or placebo for 12 months. The main outcome measures were the rate and duration of exacerbations; secondary outcomes included subject’s and physician’s severity scores (S1 and S2, respectively), the score of the Saint George’s Respiratory Questionnaire (SGRQ), and the use of reliever medications. Results: Compared to placebo, erdosteine reduced overall mean exacerbation rate by 17.1% (p=0.01) and mild exacerbation rate by 57.1% (p=0.002), but it did not change the rate of moderate/severe exacerbations. Erdosteine lowered mean exacerbation duration (-24.6%, p=0.023), an effect seen in both mild (-22.1%, p=0.039) and moderate/severe exacerbations. Erdosteine improved S1 and S2 (p= 0.022 and p=0.048 respectively), reduced the use of reliever medication (p<0.001), but not the SGRQ score. The percentage of patients with adverse events were similar in both treatment groups. Conclusions: Erdosteine reduces the rate and duration of COPD exacerbations with a placebo-like safety profile; it may represent a useful additional COPD treatment.