Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial.
BACKGROUND
Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis.


METHODS
This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival.


CONCLUSIONS
Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China.


BACKGROUND
ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013.
Jianhui
J
Qu
Zujiang
Z
Yu
Qin
Q
Li
Yongping
Y
Chen
Dedong
D
Xiang
Lin
L
Tan
Chunliang
C
Lei
Wenlin
W
Bai
Hongyan
H
Li
Qinghua
Q
Shang
Liang
L
Chen
Xiaoyu
X
Hu
Wei
W
Lu
Zhiqin
Z
Li
Da
D
Chen
Xiaodong
X
Wang
Changjiang
C
Zhang
Guangming
G
Xiao
Xun
X
Qi
Jing
J
Chen
Li
L
Zhou
Guofeng
G
Chen
Yonggang
Y
Li
Zhen
Z
Zeng
Guanghua
G
Rong
Zheng
Z
Dong
Yan
Y
Chen
Min
M
Lou
Chunping
C
Wang
Yinying
Y
Lu
Cuihong
C
Zhang
Center of Therapeutic Research for Liver Cancer, the 302 hospital of PLA, 100 Xisi Huan Middle Road, Beijing 100039, China. yongpingyang@hotmail.com.
Yongping
Y
Yang
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002681:China; D002985:Clinical Protocols; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008516:Medicine, Chinese Traditional / Q000009:adverse effects / Q000379:methods*; D008875:Middle Aged; D011446:Prospective Studies; D012107:Research Design; D013607:Tablets; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D013607:Tablets; C000599256:biejia ruangan; C413685:entecavir; D006147:Guanine