A Clinical Trial Of Antioxidant Therapy On Patients With Chronic Obstructive Pulmonary Disease

Objective:The study is aimed to investigate the efficacy of N-acetylcysteine 1200 mg(600 twice a day)in reducing the exacerbation rate in patients suffering from moderate to severe Chronic Obstructive Pulmonary Disease(COPD).Methods:To implement a prospective,randomised,double-blind,placebo-controlled,parallel groups,multi-centre study in patients with moderate to severe COPD.Patients will be randomized to study treatments for 1 year,and then will be followed on sites.All relevant medical information will be colleted.Results:We screened 1297 patients,of whom 1006 were eligible for randomization(504 to N-acetylcysteine and 502 to placebo).After 1 year,we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit(1-16 exacerbations per patient-year)and 641 acute exacerbations in 482 patients in the placebo group(1·49 exacerbations per patient-year;risk ratio 0.78,95%CI 0.67-0.90;p=0.0011).The primary endpoints showed that in the whole study group,numbers of exacerbation per patient per year reduced significantly by 22%in high dose NAC group compared with placebo group.In a stratified analysis,patients treated without ICS achieved a better outcome,with a 29%reduction of the exacerbation rate in NAC group.Although the time to first exacerbation did not show statistic difference between NAC group and Placebo group in the whole population,time to the first exacerbation was remarkably reduced in those with GOLD moderate severity,suggesting the better benefits of early prevention of AECOPD.Apart from the benefits of early intervention,our study also displayed that longer treatment period might getting better prevention effects,reduction of exacerbation was achieved by 17%after 6 months of treatment,19%after 9 months and 22%after 12 months.In terms of quality of life determined by SGRQ,symptom score reduced statistical and clinical significantly in NAC group by comparison with placebo group.Symptoms score of Quality of life determined by SGRQ reduced statistically and clinically significantly in NAC group.N-acetylcysteine was well tolerated:146(29%)of 495 patients who received at least one dose of N-acetylcysteine had adverse events(48 serious),as did 130(26%)of 495 patients who received at least one dose of placebo(46 serious).The safety issues did not show statistic difference between N-acetylcysteine group and placebo group.Conclusion:Our findings show that in Chinese patients with moderate-to-severe COPD,long-term use of N-acetylcysteine 600 mg twice daily can prevent exacerbations,especially in disease of moderate severity.Patients treated without ICS achieved a better outcome.The study also displayed that longer treatment period might get better prevention effects.N-acetylcysteine was well tolerated which shows the good safety.