High-dose N-acetylcysteine for long-term, regular treatment of early-stage chronic obstructive pulmonary disease (GOLD I–II): study protocol for a multicenter, double-blinded, parallel-group, randomized controlled trial in China

INTRODUCTION: The presence of increased oxidative stress and airway inflammation has been proven in subjects with chronic obstructive pulmonary disease (COPD). Several studies have demonstrated that drugs with antioxidant and anti-inflammatory properties such as N-acetylcysteine (NAC) can reduce the rate of exacerbations in patients with COPD. However, the beneficial effects of NAC in early-stage COPD are minimally discussed. We are investigating whether high-dose NAC has therapeutic effects in Chinese patients with early-stage COPD. METHOD AND ANALYSIS: A randomized, double-blinded, placebo-controlled, parallel-group, multicenter clinical trial is evaluating the efficacy and safety of NAC for the long-term treatment of patients with early-stage COPD at 24 centers in China. Subjects aged 40–80 years and recruited by physicians or researchers with special training will be randomized to either NAC 600 mg twice daily group or matching placebo group for 2 years. Measurements will include forced expiratory volume in 1 s (FEV(1)), the number of COPD exacerbations, health-related quality, and pharmacoeconomic analysis. DISCUSSION: Currently, there are no randomized controlled trials with high-dose N-acetylcysteine (600 mg twice daily) for patients with mild-to-moderate COPD (GOLD I–II). We designed this multicenter randomized controlled trial (RCT) to assess the effectiveness, safety, and cost-effectiveness of long-term treatment with high-dose N-acetylcysteine. The results of this trial may guide clinical practice and change the standard of early COPD management. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IIR-17012604. Registered on 07 September 2017.