Randomized Controlled Trial
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 26, 2021; 9(18): 4690-4699
Published online Jun 26, 2021. doi: 10.12998/wjcc.v9.i18.4690
Tenofovir disoproxil fumarate in Chinese chronic hepatitis B patients: Results of a multicenter, double-blind, double-dummy, clinical trial at 96 weeks
Xiao-Fan Chen, Ya-Nan Fan, Chong-Wen Si, Yan-Yan Yu, Jia Shang, Zu-Jiang Yu, Qing Mao, Qing Xie, Wei Zhao, Jun Li, Zhi-Liang Gao, Shan-Ming Wu, Hong Tang, Jun Cheng, Xin-Yue Chen, Wen-Hong Zhang, Hao Wang, Zhong-Nan Xu, Ling Wang, Jun Dai, Jing-Hang Xu
Xiao-Fan Chen, Ya-Nan Fan, Chong-Wen Si, Yan-Yan Yu, Jing-Hang Xu, Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing 100034, China
Jia Shang, Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou 450003, Henan Province, China
Zu-Jiang Yu, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Qing Mao, Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
Qing Xie, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
Wei Zhao, Department of Infectious Diseases, The Second Affiliated Hospital of Southeast University, Nanjing 210011, Jiangsu Province, China
Jun Li, Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Zhi-Liang Gao, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Shan-Ming Wu, Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201052, China
Hong Tang, Department of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Jun Cheng, Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Xin-Yue Chen, Department of International Medical, Beijing Youan Hospital, Capital Medical University, Beijing 10069, China
Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
Hao Wang, Department of Infectious Diseases, Peking University People's Hospital, Beijing 100044, China
Zhong-Nan Xu, Ling Wang, Jun Dai, Clinical Center, Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd, Nanjing 210000, Jiangsu Province, China
Author contributions: Chen XF and Fan YN wrote the article; Yu YY, Xu JH, and Si CW formatted and revised the article; Shang J, Yu ZJ, Mao Q, Xie Q, Zhao W, Li J, Gao ZL, Wu SM, Tang H, Cheng J, Chen XY, Zhang WH, and Wang H provided data from various clinical centers; Xu ZN, Wang L, and Dai J made statistics.
Supported by The 13th Five-year Science and Technology Major Project of China, on the Prevention and Treatment of Major Infectious Diseases, No. 2017ZX10202202.
Institutional review board statement: The study was reviewed and approved by the Ethics Committees of the 14 study sites, including Peking University First Hospital, China, and all procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments (approval No. 2013L01048).
Clinical trial registration statement: This study is registered at ClinicalTrials.gov. The registration identification number is NCT02287857.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Nothing to declare.
Data sharing statement: Data sets are available from the corresponding author (yyy@bjmu.edu.cn). The presented data are anonymized, and the risk of identification is low. No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing-Hang Xu, MD, PhD, Professor, Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China. ddcatjh@sina.com
Received: December 17, 2020
Peer-review started: December 17, 2020
First decision: January 7, 2021
Revised: January 24, 2021
Accepted: April 21, 2021
Article in press: April 21, 2021
Published online: June 26, 2021
Processing time: 176 Days and 4.3 Hours
Abstract
BACKGROUND

Tenofovir disoproxil fumarate (TDF) is a prodrug of a nucleotide analogue. As an antiviral drug, TDF has been proposed in the first-line treatment of chronic hepatitis B (CHB). Qingzhong, a brand name of TDF, commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd., and Viread, another brand name of TDF, commercialized by GlaxoSmithKline, have both been approved by the State Food and Drug Administration, China.

AIM

To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients.

METHODS

This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857. A total of 330 Chinese CHB patients, among which 232 were hepatitis B e antigen (HBeAg)-positive, were included in this 5-year-long, multicenter, double-blinded, double-dummy, randomized-controlled, non-inferiority phase III trial. The participants were initially randomized into two groups: Group A (n = 161), in which the participants received 300 mg Qingzhong once a day for 48 wk; and Group B, in which the participants received 300 mg Viread once a day for 48 wk. Starting from week 49, all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week. In this study, the primary endpoint was the decrease in plasma level of hepatitis B virus (HBV) DNA at the 96th week, while the secondary endpoints were suppression of HBV replication, alanine aminotransferase (ALT) normalization, HBeAg loss, and HBeAg seroconversion rates.

RESULTS

For the participants with HBeAg-positive CHB, the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B (5.77 vs 5.73 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA, HBeAg loss, and HBeAg seroconversion (71.05% vs 77.97%, 31.00% vs 27.27%, and 20.22% vs 15.79%, respectively, in Group A vs Group B; P > 0.05). For the participants with HBeAg-negative CHB, the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B (4.46 vs 4.70 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA (87.23% vs 94.12% in Group A vs Group B, respectively; P > 0.05). Finally, similar percentages of CHB patients (HBeAg-positive or HBeAg-negative) in the two groups exhibited normalization of ALT (80.14% vs 84.57% in Group A vs Group B, respectively; P > 0.05), and similar incidences of adverse events were observed (106 vs 104 in Group A vs Group B, respectively; P > 0.05).

CONCLUSION

Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.

Keywords: Chronic hepatitis B; Hepatitis B virus infection; Chronic; Tenofovir disoproxil fumarate; Randomized, controlled trial; Treatment outcomes; Noninferiority trial

Core Tip: This clinical trial compared the efficacy and safety of Qingzhong and Viread, two commercialized tenofovir disoproxil fumarate drugs, in the treatment of Chinese chronic hepatitis B (CHB) patients during a 96-wk period. The decrease in mean hepatitis B virus DNA level relative to the baseline value, the rates of hepatitis B e antigen (HBeAg) loss and HBeAg seroconversion, and the incidence of adverse events were all comparable between patients treated with the two drugs. Our results indicate that both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients.