The Efficacy and Safety of Yiqi Huoxue Huatan granule in the treatment of stable COPD with Chronic Respiratory Failure: A Randomized, Double-blind, Placebo Controlled Trial

Jia-Yi Yang; Hong-Tao Wang; Ke-Ming Zhao; Xue-Qing Yu; Dong-Hui Huang; Hui-Xian Wang; Geng-Shu Wei; Li Bai; Ya-Jing Hou; Qing-Tian Huang; Jing Hu; Hui-Zhi Zhu; Lei Wu; Xue-Chao Lu; Yun-Feng Chen; Feng Gao; Lian-Hua Su; Yang Wang; Chun-Ying Li; Su-Yun Li; Cui-Ling Feng

doi:10.1016/j.jep.2025.120228

The Efficacy and Safety of Yiqi Huoxue Huatan granule in the treatment of stable COPD with Chronic Respiratory Failure: A Randomized, Double-blind, Placebo Controlled Trial

J Ethnopharmacol. 2025 Jul 1:120228. doi: 10.1016/j.jep.2025.120228. Online ahead of print.

Authors

Jia-Yi Yang¹, Hong-Tao Wang¹, Ke-Ming Zhao², Xue-Qing Yu³, Dong-Hui Huang⁴, Hui-Xian Wang⁵, Geng-Shu Wei⁶, Li Bai⁷, Ya-Jing Hou⁷, Qing-Tian Huang⁸, Jing Hu⁸, Hui-Zhi Zhu⁹, Lei Wu¹⁰, Xue-Chao Lu¹¹, Yun-Feng Chen¹², Feng Gao¹³, Lian-Hua Su¹⁴, Yang Wang¹⁵, Chun-Ying Li¹⁶, Su-Yun Li¹⁷, Cui-Ling Feng¹⁸

Affiliations

¹ Department of Traditional Chinese Medicine, Peking University People's Hospital, Beijing, China.
² Department of Respiratory Medicine, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Liaoning, China.
³ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan, China.
⁴ Department of Respiratory Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine Zhuhai Branch, Guangdong, China; Department of Respiratory Medicine, Zhuhai City Integrated Traditional Chinese and Western Medicine Hospital, Guangdong, China.
⁵ Department of Respiratory Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine Zhuhai Branch, Guangdong, China.
⁶ Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Shaanxi University of Chinese Medicine, Shanxi, China.
⁷ Department of Respiratory and Critical Care Medicine, Shanxi Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Shanxi, China.
⁸ Pulmonology Department, Jinan Hospital of Integrated Traditional Chinese and Western Medicine, Shandong, China.
⁹ Department of Respiratory Medicine, The First Affiliated Hospital of Anhui University of Chinese Medicine, Anhui, China.
¹⁰ Department of Respiratory Medicine, Hebei Provincial Hospital of Traditional Chinese Medicine, Hebei, China.
¹¹ Department of Respiratory and Critical Care Medicine, Qingdao Hai Ci Medical Group, Shandong, China.
¹² Department of Respiratory and Critical Care Medicine, Chengdu Hospital of Integrated Traditional Chinese and Western Medicine, Sichuan, China.
¹³ Department of Respiratory Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
¹⁴ Pulmonology Department, Beijing Fangshan District Hospital of Traditional Chinese Medicine, Beijing, China.
¹⁵ Department of Respiratory Medicine, Changping District Hospital of Traditional Chinese Medicine, Beijing, China.
¹⁶ Pulmonology Department, Hainan Provincial Hospital of Traditional Chinese Medicine, Hainan, China.
¹⁷ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan, China. Electronic address: lisuyun2000@126.com.
¹⁸ Department of Traditional Chinese Medicine, Peking University People's Hospital, Beijing, China. Electronic address: fengcuiling@sina.com.

PMID: 40609812
DOI: 10.1016/j.jep.2025.120228

Abstract

Ethnopharmacological relevance: Yiqi Huoxue Huatan granule is an empirical traditional Chinese medicine formula that has been widely used for the treatment of respiratory diseases. However, whether Yiqi Huoxue Huatan granule has a therapeutic effect on patients with stable COPD complicated with chronic respiratory failure remain unclear.

Aim of the study: To evaluate the efficacy and safety of Yiqi Huoxue Huatan granule in treating this population.

Material and methods: This is a double-blind randomized clinical trial, conducted at 15 health centers in China from October 2019 to December 2021. 372 participants aged 40-80, were enrolled. All had been diagnosed with stable COPD and exhibited PaO2<60mmHg and PaCO2>50mmHg during quiet breathing at sea level according to arterial blood gas analysis results. Eligible patients were randomly assigned to the treatment group (Yiqi Huoxue Huatan granule combined with western medicine), or the control group (a placebo together with western medicine). The treatment phase lasted 52 weeks, followed by a 52-week follow-up. The primary outcomes were mortality and the frequency of acute exacerbations of COPD.

Results: 186 patients in the treatment group and 186 in the control group were for intention-to-treat analysis. Among them, a total of 317 patients were included in the per protocol set. Yiqi Huoxue Huatan granule combined with western medicine was found to reduce all-cause mortality by 5.62%. Specifically, there were 11 deaths (6.96%, 95% CI -2.95% to 10.97%) in the treatment group compared to 20 (12.58%, 95% CI -7.37% to 17.79%) in the control group, P=0.131. Moreover, the frequency of acute exacerbations was significantly reduced in the follow-up period (1.04±1.25 [95% CI -0.84 to 1.24] in the treatment group vs 1.24±1.40 [95% CI -1.02 to 1.46] in the control group, P=0.183 during treatment period, while 0.71±1.01 [95% CI -0.54 to 0.87] in the treatment group vs 1.03±1.22 [95% CI -0.83 to 1.23] in the control group, P=0.016 during follow-up period). For safety analysis, six of 186 patients in the treatment group and three of 186 patients in the control group suffer adverse events.

Conclusions and relevance: Yiqi Huoxue Huatan granule is proved to be able to reduce the mortality and the frequency of acute exacerbations of COPD. Thus, it can serve as a reasonable therapeutic option for patients with stable COPD complicated by chronic respiratory failure.

Trial registration: ClinicalTrials.gov Identifier: NCT04208581.

Keywords: Chronic Obstructive Pulmonary Disease; Chronic Respiratory Failure; Yiqi Huoxue Huatan Granule.

Associated data

ClinicalTrials.gov/NCT04208581