• Jianwen Guo, Xiaoying Chen, Manli Wu, Dou Wang, Yang Zhao, Qiang Li, Guanghai Tang, Fengyuan Che, Zhangyong Xia, Zai Liang, Liu Shi, Qiuhua Jiang, Yajie Chen, Xiaoqiu Liu, Xinwen Ren, Menglu Ouyang, Borui Wang, Shoujiang You, Laurent Billot, Xia Wang, Zhenchuan Liu, Hongyan Jing, Wei Meng, Song Tian, Enzhi Liu, Yong Xiang, Xiaoping Tang, Tingting Xie, Wanzhen Cui, Yanwen Zheng, Jiamin Cao, Jingbei Zhang, Zehuai Wen, Tao Huang, Lixin Wang, Chao You, Suyue Pan, Yefeng Cai, Yun Lu, Graeme J Hankey, Rustam Al-Shahi Salman, Craig S Anderson, Lili Song, and CHAIN investigators.
• State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Research Team of Prevention and Treatment of Cerebral Hemorrhage Applying Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; The Second Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. Electronic address: jianwen_guo@qq.com.
• Lancet. 2024 Nov 12.

BackgroundThere are few proven treatments for acute spontaneous intracerebral haemorrhage, and they all target reducing expansion of the haematoma. The traditional Chinese medicine FYTF-919 (Zhongfeng Xingnao) in an oral solution is comprised of several Chinese herbs that are widely used to treat patients with intracerebral haemorrhage in China on the understanding that they enhance resorption of the haematoma and reduce neuroinflammation. We aimed to provide a reliable assessment of the safety and efficacy of FYTF-919 in patients with moderate to severe acute intracerebral haemorrhage.MethodsWe did a pragmatic, multicentre, randomised, double-blind, placebo-controlled trial at 26 hospitals in China. We enrolled adults (age ≥18 years) with a diagnosis of symptomatic spontaneous intracerebral haemorrhage (confirmed by brain imaging) within 48 h after the onset of symptoms (or last seen well), which resulted in moderate to severe neurological impairment defined by scores of at least 8 on the National Institute of Health Stroke Scale or between 7 and 14 inclusive on the Glasgow Coma Scale. Randomisation (1:1) was via a central internet-based system with a block grouping method stratified by provincial location of the hospital, severity of neurological impairment, and site of the haematoma in the brain. FYTF-919 and the placebo were masked through consistency in appearance, smell, taste, and other aspects. Participants were allocated to receive 33 mL (or 25 mL via a nasogastric tube if a participant's swallowing was impaired) of either oral liquid FYTF-919 or matching placebo administered at least 30 min after a meal every 8 h (or 6 h via nasogastric tube) over 24 h for 28 days. The primary efficacy outcome was the utility weighted modified Rankin Scale (a seven-level ordinal scale that ranges from 0 [no symptoms] to 6 [death], in which the utility weights of 0·97, 0·88, 0·74, 0·55, 0·20, -0·19, and 0·00 were assigned to the seven levels respectively, with higher scores indicating a better outcome according to the participants' perspective) at 90 days analysed in a general linear model with adjustment for baseline factors. We did several adjusted and sensitivity analyses. Primary analyses were assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT05066620 and is complete.FindingsBetween Nov 24, 2021, and Dec 28, 2023, of 9000 patients screened, 1648 were randomly assigned to treatment, 817 to the FYTF-919 group and 831 to the placebo group. Before receiving any treatment two patients in the FYTF-919 group and five patients in the placebo group immediately withdrew their consent leaving 1641 participants with available primary outcome data in the intention-to-treat population, 815 in the FYTF-919 group and 826 in the placebo group. 1242 (75·7%) participants consumed 80% or more of the study medication and 994 (60·6%) consumed all of it within 28 days. Mean utility weighted modified Rankin Scale scores at 90 days were 0·44 in the FYTF-919 group and 0·44 in the placebo group (difference 0·01, 95% CI -0·02 to 0·04; p=0·63). The neutral result was consistent in adjusted and sensitivity analyses. There was no significant difference in serious adverse events.InterpretationThis large, randomised, placebo-controlled, double-blind, clinical trial showed no effect of the traditional Chinese medicine herbal compound FYTF-919 on functional recovery, survival, and health-related quality of life in patients with moderate to severe intracerebral haemorrhage. The results reaffirm the need for methodologically rigorous, randomised controlled trials to evaluate the effectiveness of existing therapies, including traditional Chinese medicines that are already in widespread use throughout the world.FundingKey-Area Research and Development Program of Guangdong Province.Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

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