Efficacy and safety of Chinese medicine in treating risk window of AECOPD: A multicenter randomized controlled trial.

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) significantly accelerate disease progression and substantially increase mortality risk. The risk window of AECOPD (AECOPDRW) represents a time between acute exacerbation and recovery to a stable stage. Chinese medicine (CM) has shown significant therapeutic efficacy in COPD but CM treatment for AECOPDRW has not been validated by high-quality clinical studies.

Purpose: To assess the clinical effect of CM syndrome differentiation treatment for patients with AECOPDRW.

Study Design: A multicenter, randomized, double-blind, placebo-controlled parallel trial.

Methods: 336 eligible participants were included to the study. Both groups were based on the conventional treatment as the baseline therapy. The experimental group was administered Chinese herbal medicine granules based on CM syndrome differentiation, whereas the control group received a placebo in the form of Chinese herbal medicine granules. The intervention course lasted for 8-week, while the follow-up for 26-week. Primary outcomes were incidences of acute exacerbation and COPD Assessment Test (CAT) scores recorded during AECOPDRW. Secondary outcomes were the timing of the first acute exacerbation, incidence of exacerbations, acute exacerbation readmission rate, severity of exacerbation, and CAT scores during follow-up, pulmonary function, mMRC scale, clinical symptom scale, and the quality of life assessment tools.

Results: At 8-week, the risk of acute exacerbations and CAT score were significantly reduced in the experimental group between-group analysis with a risk ratio (RR) of 0.375(95 % confidence interval [CI]: 0.150 to 0.935; p = 0.027), and a mean difference (MD) of -2.476 score (95 % CI: -3.281 to -1.671; p < 0.001). At 26-week, experimental group showed statistically lower risk of acute exacerbation between-group analysis (RR: 0.519; 95 % CI: 0.282 to 0.953; p = 0.030). The first exacerbation time in the experimental group (97.63 ± 35.90) was statistically longer than in the control group (66.11 ± 25.25) (MD: 31.517 (95 % CI: 14.720 to 48.314; p < 0.001). The rates of acute exacerbation readmission were similar for both the groups during the risk window and follow-up period. After 26 weeks of follow-up, experimental group CAT score was reduced by 2.046 between-group analysis (p < 0.001). Furthermore, during the whole study, the experimental group showed significantly reduced in mMRC score, as well as FEV and FVC values (all p < 0.05). During study period, the experimental group had a significant reduce in clinical symptom scores, including cough, expectoration, and fatigue, than the control group (p < 0.05). Regarding to SGRQ, mCOPD-PRO and mESQ-COPD, our results demonstrated that CM had better advantages in many aspects.

Conclusion: Treatment of AECOPDRW with CM showed high efficacy and safety in significantly reducing further incidences of acute exacerbation, prolonging the interval to the initial acute exacerbation, alleviating the clinical symptoms, and improving the quality of life.