Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial.

Yong-an YE; Xiao-ke LI; Da-qiao Zhou; Xiao-ling Chi; Qin LI; Li Wang; Bing-jiu LU; De-wen Mao; Qi-kai WU; Xian-bo Wang; Ming-xiang Zhang; Jing-dong Xue; Yong LI; Wei LU; Jian-chun Guo; Feng Jiang; Xin-wei Zhang; Hong-bo DU; Xian-zhao Yang; Hui Guo; Da-nan Gan; Zhi-guo LI

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Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial.

Author: Yong-An YE ¹ ; Xiao-Ke LI ² ; Da-Qiao ZHOU ³ ; Xiao-Ling CHI ⁴ ; Qin LI ⁵ ; Li WANG ⁶ ; Bing-Jiu LU ⁷ ; De-Wen MAO ⁸ ; Qi-Kai WU ⁹ ; Xian-Bo WANG ¹⁰ ; Ming-Xiang ZHANG ¹¹ ; Jing-Dong XUE ¹² ; Yong LI ¹³ ; Wei LU ¹⁴ ; Jian-Chun GUO ¹⁵ ; Feng JIANG ² ; Xin-Wei ZHANG ¹⁶ ; Hong-Bo DU ² ; Xian-Zhao YANG ² ; Hui GUO ¹⁷ ; Da-Nan GAN ² ; Zhi-Guo LI ²
Author Information

1. Institute of Liver Diseases, Beijing University of Chinese Medicine, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Beijing, 100700, China. yeyongan@vip.163.com.
2. Institute of Liver Diseases, Beijing University of Chinese Medicine, Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine, Beijing, 100700, China.
3. Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, 518033, China.
4. Department of Hepatology, Guangdong Hospital of Traditional Chinese Medicine, Guangzhou, 510006, China.
5. Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
6. Department of Hepatology, Public Health Clinical Center of Chengdu, Chengdu, 610066, China.
7. Department of Hepatology, Liaoning Hospital of Traditional Chinese Medicine, Shenyang, 110032, China.
8. Department of Hepatology, the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, China.
9. Department of Hepatology, the Third People's Hospital of Shenzhen, Shenzhen, Guangdong Province, 518112, China.
10. Department of Hepatology, Beijing Ditan Hospital, Beijing, 100015, China.
11. Department of Hepatology, the Sixth People's Hospital of Shenyang, Shenyang, 110006, China.
12. Department of Hepatology, Shaanxi Hospital of Traditional Chinese Medicine, Xi'an, 710003, China.
13. Department of Hepatology, Shandong Hospital of Traditional Chinese Medicine, Jinan, 250011, China.
14. Department of Hepatology, the Second People's Hospital of Tianjin, Tianjin, 300000, China.
15. Department of Hepatology, Xixi Hospital of Hangzhou, Hangzhou, 310023, China.
16. Department of Hepatology, 302 Military Hospital of China, Beijing, 100039, China.
17. Department of Hepatology, the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300000, China.
Publication Type:Journal Article
Keywords: Chinese herbal medicine; Tiaogan- Yipi Granule; Tiaogan-Jianpi-Jiedu Granule; chronic hepatitis B; protocol; randomized-controlled trial
From: Chinese journal of integrative medicine 2018;24(9):653-660
CountryChina
Language:English
Abstract:
BACKGROUNDThe domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.
METHODSThe study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment.
DISCUSSIONThe study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).