Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study

Abstract

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.

Impact of erdosteine on chronic bronchitis and COPD: A meta-analysis

“…Erdosteine is currently the only mucolytic/antioxidant agent that has been evaluated in patients with frequent exacerbations, those that have experienced two or more COPD exacerbations requiring medical intervention in the previous 12 months. The recent Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD (RESTORE) study [13], which enrolled 445 frequent exacerbators,…”

“…Results obtained from 1,278 patients (52.66% in the active treatment group, 47.34 in the control group) were selected from 10 published studies, including 6 studies on chronic bronchitis [26][27][28][29][30][31], 3 studies on COPD [12,13,32], and 1 study on patients suffering from both chronic bronchitis and COPD [33]. Eight studies had a Jadad score ≥3 [12, 13, 26-29, 31, 32], and 2 studies had a Jadad score <3 [30,33].…”

“…In light of these criticisms and the recent publication of two further articles focused on the prevention of acute exacerbations of COPD with erdosteine [12,13], we have carried out a quantitative synthesis via meta-analysis of the currently available data with this drug in order to provide consistent and homogeneous findings that may help better clarify the real impact of erdosteine in improving the clinical score of patients with chronic bronchitis and/or COPD, and the use of this drug in preventing chronic bronchitis/COPD exacerbations.…”

<p>Pharmacokinetics and safety of revefenacin in subjects with impaired renal or hepatic function</p>

“…1 Many patients with COPD are older or have comorbid conditions that can be associated with renal or hepatic impairment. 2,3 Revefenacin is a once-daily, long-acting, lung-selective muscarinic receptor antagonist formulated as a nebulized inhalation solution for use with a standard jet nebulizer for treatment of patients with COPD. Nebulized therapies are of particular interest in patients with poor hand/breath coordination and/or respiratory muscle weakness that limits their use of dry powder inhalers and pressurized metered-dose inhalers.…”

Mucolytics for COPD: negotiating a slippery slope towards proof of efficacy

“…The active metabolites of erdosteine exhibit mucolytic and free radical scavenging activity [10] and previous small clinical trials have suggested some benefit in treating acute exacerbations of COPD with erdosteine [11,12]. In this issue of the European Respiratory Journal, DAL NEGRO et al [13] report results from a Phase-III controlled clinical trial that enrolled patients with GOLD stage II-III COPD and randomised them to receive erdosteine (300 mg twice daily) or a placebo for 12 months in addition to their usual COPD therapy. The primary outcome was the number of acute exacerbations (mild, moderate or severe) during the study.…”