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Chinese Journal of Integrative Medicine

, Volume 24, Issue 9, pp 653–660 | Cite as

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 YeEmail author
  • 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
Original Article
  • 59 Downloads

Abstract

Background

The 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 (调肝益脾颗粒, TGYP) or Tiaogan-Jianpi-Jiedu Granule (调肝健脾解毒颗粒, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.

Methods

The 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.

Discussion

The 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).

Keywords

chronic hepatitis B Chinese herbal medicine Tiaogan-Jianpi-Jiedu Granule Tiaogan- Yipi Granule protocol randomized-controlled trial 

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Supplementary material

11655_2018_3011_MOESM1_ESM.pdf (79 kb)
Appendix 1

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Copyright information

© Chinese Association of the Integration of Traditional and Western Medicine 2018

Authors and Affiliations

  • Yong-an Ye
    • 1
    Email author
  • Xiao-ke Li
    • 1
  • Da-qiao Zhou
    • 2
  • Xiao-ling Chi
    • 3
  • Qin Li
    • 4
  • Li Wang
    • 5
  • Bing-jiu Lu
    • 6
  • De-wen Mao
    • 7
  • Qi-kai Wu
    • 8
  • Xian-bo Wang
    • 9
  • Ming-xiang Zhang
    • 10
  • Jing-dong Xue
    • 11
  • Yong Li
    • 12
  • Wei Lu
    • 13
  • Jian-chun Guo
    • 14
  • Feng Jiang
    • 1
  • Xin-wei Zhang
    • 15
  • Hong-bo Du
    • 1
  • Xian-zhao Yang
    • 1
  • Hui Guo
    • 16
  • Da-nan Gan
    • 1
  • Zhi-guo Li
    • 1
  1. 1.Institute of Liver Diseases, Beijing University of Chinese MedicineDongzhimen Hospital affiliated to Beijing University of Chinese MedicineBeijingChina
  2. 2.Department of HepatologyShenzhen Traditional Chinese Medicine HospitalShenzhen, Guangdong ProvinceChina
  3. 3.Department of HepatologyGuangdong Hospital of Traditional Chinese MedicineGuangzhouChina
  4. 4.Department of HepatologyMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouChina
  5. 5.Department of HepatologyPublic Health Clinical Center of ChengduChengduChina
  6. 6.Department of HepatologyLiaoning Hospital of Traditional Chinese MedicineShenyangChina
  7. 7.Department of Hepatologythe First Affiliated Hospital of Guangxi University of Chinese MedicineNanningChina
  8. 8.Department of Hepatologythe Third People’s Hospital of ShenzhenShenzhen, Guangdong ProvinceChina
  9. 9.Department of HepatologyBeijing Ditan HospitalBeijingChina
  10. 10.Department of Hepatologythe Sixth People’s Hospital of ShenyangShenyangChina
  11. 11.Department of HepatologyShaanxi Hospital of Traditional Chinese MedicineXi’anChina
  12. 12.Department of HepatologyShandong Hospital of Traditional Chinese MedicineJinanChina
  13. 13.Department of Hepatologythe Second People’s Hospital of TianjinTianjinChina
  14. 14.Department of HepatologyXixi Hospital of HangzhouHangzhouChina
  15. 15.Department of Hepatology302 Military Hospital of ChinaBeijingChina
  16. 16.Department of Hepatologythe First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjinChina

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