针对相对年轻患者的稳定慢性阻塞性肺疾病的Astragalus-containing复方：一项多中心、随机、双盲、安慰剂对照试验的研究方案

【BACKGROUND】Chronic obstructive pulmonary disease (COPD) increasingly affects relatively younger, working-age adults, in whom impaired physical function can compromise work, family responsibilities, and quality of life. This study aims to evaluate the efficacy and safety of an Astragalus-containing compound formula as an adjunct to protocol-specified background Western maintenance therapy in patients with stable COPD, with particular interest in its effects among relatively younger, working-age patients.

【METHODS】This multicenter, randomized, double-blind, placebo-controlled trial includes patients aged 40-75 years with stable COPD, Global Initiative for Chronic Obstructive Lung Disease grades 2-4, at least two moderate exacerbations or one exacerbation-related hospitalization during the previous 12 months, and the traditional Chinese medicine (TCM) pattern of lung-kidney qi deficiency. An exploratory age-focused analysis will evaluate participants aged 40-60 years. The intervention is a fixed 12-herb Astragalus-containing compound formula. Eligible participants must have received one of the protocol-specified stable-dose inhaled maintenance regimens for at least 3 consecutive months before screening. Participants are centrally randomized 1:1 through an Interactive Web Response System (IWRS), with stratification by study center, to receive either a fixed 12-herb Astragalus-containing compound formula or matching placebo for 48 weeks in addition to background therapy. Primary outcomes are acute exacerbation frequency, lung function assessed by forced expiratory volume in one second, forced vital capacity, and their ratio, and physical fitness assessed by six-minute walk distance (6MWD), muscle strength, flexibility, and balance. Secondary outcomes include the modified Medical Research Council (mMRC) dyspnea scale, COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), TCM syndrome score, and Epworth Sleepiness Scale (ESS). Assessments will be conducted at baseline and at weeks 4, 12, 24, 36, and 48. Primary efficacy analyses will be conducted in the full analysis set (FAS), following the intention-to-treat (ITT) principle, using prespecified negative binomial regression and linear mixed-effects models, with per-protocol (PP) analyses performed as sensitivity analyses.

【DISCUSSION】This trial is designed to evaluate whether the compound formula provides additional long-term benefits in reducing exacerbations and improving physical function in relatively younger and working-age patients with stable COPD.

【TRIAL REGISTRATION】Drug Clinical Trial Registration and Information Disclosure Platform of the National Medical Products Administration (NMPA), China, registration No. CTR20232692.