Fuzheng Huayu tablets for treating pulmonary fibrosis in post-COVID-19 patients: A multicenter, randomized, double-blind, placebo-controlled trial

Fei Jing ¹ Wei Wang ² Jia Ke ³ Tingrong Huang ⁴ Bo Jiang ⁵ Qiwu Qiu ⁶ Jihan Huang ⁷ Songhua Zhan ⁸ Zhang Wei ⁹ Hui Wu ¹⁰ Wen Su ¹¹ Jiawen Feng ¹ Yuan Peng ¹ Zhimin Zhao ¹ Feng Xing ^1* Chenghai Liu ^1*

• ¹ Institute of Liver diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
• ² Hubei University of Chinese Medicine, Wuhan, Hubei Province, China
• ³ Department of Respiratory, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Wuhan, Hebei Province, China
• ⁴ Huangshi Hospital of Traditional Chinese Medicine, Huangshi, China
• ⁵ Department of Traditional Chinese Medicine, Wuhan Third Hospital, Wuhan, Hebei Province, China
• ⁶ Department of Infectious Diseases, Jingmen First People's Hospital, Jingmen, China
• ⁷ Center for Drug Clinical Research, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
• ⁸ Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
• ⁹ Department of Respiratory, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
• ¹⁰ Department of Traditional Chinese Medicine, Wuhan Integrated TCM & Western Medicine Hospital, Wuhan, Hebei Province, China
• ¹¹ Office of Academic Research, Wuhan Integrated TCM & Western Medicine Hospital, Wuhan, Hebei Province, China

Background: Effective therapies for pulmonary fibrosis caused by coronavirus disease and other etiologies are lacking. Our previous studies demonstrated that Fuzheng Huayu tablet (FZHY), a traditional Chinese medicine known for its anti-liver fibrotic properties, can improve lung function in patients with chronic obstructive pulmonary disease and attenuate bleomycin-induced pulmonary fibrosis in rats. Purpose: This study aimed to evaluate the efficacy and safety of FZHY in post-COVID-19 pulmonary fibrosis. Methods: A multi-center, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy of a 24-week treatment with FZHY, combined with vitamin C and respiratory function rehabilitation, for treating pulmonary fibrosis in discharged convalescent COVID-19 patients. The primary outcome was the regression rate of pulmonary fibrosis assessed by the high-resolution computed tomography scores and lung function improvement (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], and FEV1/FVC) after 24 weeks. Secondary outcomes included the 6-minute walk distance, improvement in pulmonary inflammation, clinical symptoms, and quality of life.Results: This study included 142 patients, who were randomized to the FZHY (n = 72) and placebo groups (n = 70). By week 24, the regression rates of pulmonary fibrosis in the FZHY and placebo groups were 71.2% and 49.2%, respectively (p = 0.01). Limited spirometry data revealed higher FEV1/FVC in the FZHY group than in the placebo group at week 8 ([87.7 ± 7.2] % vs. [82.7 ± 6.9] %; p = 0.018). The regression rates in pulmonary inflammation in the FZHY and placebo groups were 83.8% and 68.8%, respectively (p = 0.04). At week 4, the increase in 6-minute walking distance was greater in the FZHY group than in the placebo group ([41.4 ± 64.1] m vs. [21.8 ± 50.3] m; p = 0.05). However, no significant differences were observed between the groups in the improvement rate of clinical symptoms, quality of life-BREF, patient health questionnaire-9, or generalized anxiety disorder-7 scores (p > 0.05). No drug-related adverse events were reported in the FZHY group.FZHY attenuates post-COVID-19 pulmonary fibrosis, with good safety profiles.