Hepatitis B, ChronicNCT05937178

Real-world Study Optimizing Nucleotide-analogues

An observational study of Hepatitis B, Chronic, run by Huashan Hospital at 44 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Trial summary

The goal of this multicenter, observational, prospective study is to observe and compare different anti-viral treatment strategies in a real-world cohort of patients with CHB managed in routine clinical settings in China. The main questions it aims to answer are: 1. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Hepatitis B, Chronic
What is being tested?: ETV/TAF/TDF/TMF/IFN and ETV/TAF/TDF/TMF
How many people: 20,000 participants
Where: 44 sitesChina
Study dates: 31 Jan 2023to 31 Jan 2029
Phase: Observational
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Study population: Patients with chronic hepatitis B will receive the first-line antiviral therapy

Who may be able to join

CHB defined as positive hepatitis B surface antigen at least 6 months, or HBV-related histological changes within 1 year if HBsAg positive less than 6 months.
Age between 18-80 years.
Patient who reads and signs informed consent.
Meet any conditions of the group listed below
Group A-naïve and meeting the conditions that are recommended to initiate treatment in 2022 Chinese Guideline, but not in 2019 Chinese Guideline (observe-plan to treat or control-plan to follow-up) :
HBV DNA positive, ALT is continuously upper limit of normal (male 30 U/L, female 19 U/L) B. HBeAg positive, HBV DNA≤2×10^7 IU/ml; HBeAg negative, HBV DNA≥2×10^3 IU/ml C. Meet any of the conditions listed below

Show all 11Show fewer

Age>30 years, and have a family history of cirrhosis or HCC, TE indicates no significant fibrosis;
Family history of cirrhosis or HCC, and ≤30 years, TE indicates no significant fibrosis;
TE indicates significant fibrosis, and ≤30 years, without family history of cirrhosis or HCC
Group B-naïve and meeting the conditions that are recommended to initiate treatment in both 2019 and 2022 Chinese Guidelines, but not in EASL or AASLD guideline (observe-plan to treat or control-plan to follow-up) :
Without cirrhosis, HBV DNA≤2000 IU/ml, ALT>1 ULN； B. Without cirrhosis, HBV DNA>2000 IU/ml, 1 ULN<ALT≤2 ULN； C. Without cirrhosis, normal ALT, >30 years, have a family history of cirrhosis or HCC, or TE indicates significant fibrosis; D. Without cirrhosis, HBV DNA 20-2000 IU/ml Group C-experienced and partial response (1. switch another first-line NA; 2. add-on another first-line NA; 3. switch another first-line NA and add-on peginterferon alpha; 4. continue the original plan) Treatment experienced patient who has received a first-line nucleos(t)ide analogue(NA) monotherapy for at least 48 weeks, i.e., entecavir, tenofovir disoproxil or tenofovir alafenamide, tenofovir amibufenamide, and has partial response. They plan to continue or change the therapy

Who cannot join

Have poor compliance;
Received contraindicated concomitant drugs (subjects receiving prohibited drugs will need at least 30 days of washing out period) and known hypersensitivity reactions to the study drug, metabolites, or formulated excipients;
Any other clinical symptoms or previous treatment that the investigator considers that the individual subject is not suitable for this study or cannot comply with the administration requirements

Trial locations and contacts

44 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Wenghong Zhang, MD contact

13801844344

zhangwenhong@fudan.edu.cn

City, postcode or hospital

Sites recruiting now only

44 sites in 1 country

China44 sites, 44 recruiting

Beijing YouAn Hospita
Beijing, Beijing Municipality, 100000
Bin Xu, Dr, 13716830822, xubin1016@126.com
Not yet recruiting
Peking University First Hospital
Beijing, Beijing Municipality, 100000
Gui Wang, Dr, 13911405123, john131212@hotmail.com
Recruiting
Peking University People's Hospital
Beijing, Beijing Municipality, 100000
Huiying Rao, Dr, 13621390945, rao.huiying@163.com
Not yet recruiting
the First Bethune Hospital Of Jilin University
Changchun, Jilin, 130000
Yanhang Gao, Dr, 15804303019, yanhang@mail.jlu.edu.cn
Not yet recruiting
the Second Xiangya Hospital of Central South University
Changsha, Hunan, 430100
Yongfang Jiang, Dr, 13875858624, Jiangyongfang@hotmail.com
Not yet recruiting
Xiangya Hospital Central South University
Changsha, Hunan, 430100
Yan Huang, Dr, 13874854142, rhyan@126.com
Not yet recruiting
Sichuan Provincial People's Hospital
Chengdu, Sichuan, 610000
Xinxiang Yang, Dr, 18981838297, 719525383@qq.com
Not yet recruiting
West China Hospital of Sichuan University
Chengdu, Sichuan, 610000
Zhiyong Zong, Dr, 18980601643, zongzhiy@scu.edu.cn
Not yet recruiting
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400000
Dachuan Cai, Dr, 13883596197, cqmucdc@cqmu.edu.cn
Not yet recruiting
the Southwest Hospital of AMU
Chongqing, Chongqing Municipality, 400000
Qing Mao, Dr, 13594180020, qingmao@tmmu.edu.cn
Not yet recruiting
First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350000
Yueyong Zhu, Dr, 13950233535, zhuyueyong@fjmu.edu.cn
Not yet recruiting
The Affiliated Hospital Of Guizhou Medical University
Guiyang, Guizhou, 55000
Quan Zhang, Dr, 18685183363, quanzhangx@163.com
Not yet recruiting
The Second Affiliated Hospital of Harbin Medical University
Ha’erbin, Ha'erbin, 150000
Shuchen Li, Dr, 15546328855, shuchenli1964@126.com
Not yet recruiting
Hainan General Hospital
Haikou, Hainan, 570100
Feng Lin, Dr, 13976081338, lin_fengn@126.com
Not yet recruiting
Shulan (Hangzhou) Hospital
Hangzhou, Zhejiang, 310000
Hainv Gao, Dr, 13957163067, hainv.gao@shulan.com
Not yet recruiting
Anhui Provincial Hospital
Hefei, Anhui, 230000
Lei Li, Dr, 18905518525, lilei0403@163.com
Not yet recruiting
The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, 230000
Yufeng Gao, Dr, 13956938032, aygyf@126.com
Not yet recruiting
Shandong Provincial Hospital Affiliated to Shandong First Medical University
Jinan, Shandong, 250000
Wanhua Ren, Dr, 13953105950, renwanhua001@163.com
Not yet recruiting
The Second Hospital of Shandong University
Jinan, Shandong, 250000
Tao Li, Dr, 17660080982
Not yet recruiting
First People's Hospital of Yunnan Province
Kunming, Yunnan, 650000
Jiawei Geng, Dr, 13888757766, jia_wei_geng@163.com
Not yet recruiting
the First Hospital of Lanzhou University
Lanzhou, Gansu, 730000
Xiaorong Mao, Dr, 13919157938, mxr2013@126.com
Not yet recruiting
Third Affiliated Hospital, Sun Yat-Sen University
Meizhou, Xiamen, 514000
Zhiliang Gao, Dr, 13902263533, gaozl@mail.sys
Not yet recruiting
the First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330000
Xiaoping Wu, Dr, 13330122823, wuxiaoping2823g@aliyun.com
Not yet recruiting
Jiangsu Province Hospital
Nanjing, Jiangsu, 210000
Chuanlong Zhu, Dr, 17714316539, zhuchuanlong@jsph.org.cn
Not yet recruiting
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210000
Jie Li, Dr, 15863787910, lijier@sina.com
Not yet recruiting
the Second Hospital of Nangjing
Nanjing, Jiangsu, 210000
Yongfeng Yang, Dr, 13951990210, yyf1997@163.com
Not yet recruiting
First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, 530000
Boming Liao, Dr, 13086713908, 2531007428@qq.com
Not yet recruiting
No. 6 People's Hospital of Qingdao
Qingdao, Shandong, 266000
Wei Gou, Dr, 15666687727, gwqd1234@163.com
Not yet recruiting
Ruijin Hospital
Shanghai, Shanghai Municipality, 200000
Qing Xie, Dr, 13651804273, xieqingrjh@163.com
Not yet recruiting
Huashan Hospital
Shanghai, 200040
Wenhong Zhang, Professor, 13801844344, zhangwenhong@fudan.edu.cn
Feng Sun, doctor, 15921403893, aaronsf1125@126.com
Recruiting
Shengjing Hospital of China Medical University
Shenyang, Liaoning, 110000
Yang Ding, Dr, 13332434847, yding0903@sina.com
Not yet recruiting
the Third Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050000
Caiyan Zhao, Dr, 18533112898, zhaocy2005@163.com
Not yet recruiting
First Hospital of Shanxi Medical University
Taiyuan, Shanxi, 030000
Liaoyun Zhang, Dr, 13603518852, zlysgzy@163.com
Not yet recruiting
Tianjin Second People's Hospital
Tianjin, Tianjin Municipality, 300000
Jia Li, Dr, 13302106853, 1862263700@163.com
Not yet recruiting
Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine
Ürümqi, Xinjiang Uygur Autonomous Region, 830000
Xiaozhong Wang, Dr, 13809950758, wxz125@sina.com
Not yet recruiting
Renmin Hospital of Wuhan University
Wuhan, Hubei, 430000
Zuojiong Gong, Dr, 13971687857, zjgong@163.com
Not yet recruiting
Tongji Hospital
Wuhan, Hubei, 430000
Qin Ning, Dr, 13971521450, qning@vip.sina.com
Not yet recruiting
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430000
Xin Zheng, Dr, 18602724981, xin11@hotmail.com
Not yet recruiting
Tangdu Hospital, The Fourth Military Medical University
Xi'an, Shaanxi, 710000
Jianqi Lian, Dr, 13571892829, lianjq@fmmu.edu.cn
Not yet recruiting
the First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710000
Yingren Zhao, Dr, 13509187086, zhaoyingren@xjtu.edu.cn
Not yet recruiting
Xiamen Hospital of Traditional Chinese Medicine
Xiamen, Fujian, 361000
Qingfa Ruan, Dr, 15305045958, ruanqingfa@aliyun.com
Not yet recruiting
the Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221000
Xuebing Yan, Dr, 18052268128, yxbxuzhou@126.com
Recruiting
Henan Provincial People's Hospital
Zhengzhou, Henan, 450000
Yi Kang, Dr, 13938553839, wwhhslek@126.com
Not yet recruiting
The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
Zhengzhou, Henan, 450000
Guangwei Liu, Dr, 13673627502, Liuguangwei1975@163.com
Not yet recruiting

Other trials in China

About this study

Official title: A Real-world Study of Optimizing Nucleotide-analogues-based Treatment for Chronic Hepatitis B

To evaluate the benefits of initiating first-line nucleos(t)ide analogue in patients with chronic HBV infection who are recommended in the updated Chinese Guideline 2022, but not recommended in the Chinese Guideline 2019.
To evaluate the Chinese Guideline recommends initiation of treatment, but at least one foreign authoritative guideline (eg. AASLD, EASL) does not recommend the benefit of initiating first-line nucleos(t)ide analogue in patients with chronic HBV infection who initiate treatment.
To compare the treatment effect of different alternatives with patients who have partial response after treatment with first-line nucleos(t)ide analogues.

Read the detailed description

REASON is a multicenter, observational, prospective study to explore an optimal anti-viral treatment in a real-world cohort of patients with CHB managed in routine clinical settings in China. The study will enroll treatment-naïve or treatment-experienced patients ≥18 and ≤80 years of age with hepatitis B s antigen positive. The treatment-experienced patients must be treated with monotherapy ETV/TDF/TAF/TMF continuously for a minimum of 48 weeks before enrollment. The treatment of participants will be decided before the screening by doctors based on the situation and patient's intention. When eligible patients are included in this study, no extra intervention will be conducted and only clinical data are collected and observed. Participants will enter different observation groups when they meet the eligibility criteria of each group listed below: Group A：treatment-naive, and meeting the conditions that are recommended to initiate treatment in 2022 Chinese Guideline but not in 2019 Chinese Guideline; Group B：treatment-naive, meeting the conditions that are recommended to initiate treatment in both 2019 and 2022 Chinese guideline, but not in AASLD/EASL guidelines; Group C: treatment-experienced and with partial response. The primary efficacy endpoint was the proportion of patients with HBV DNA less than 20 IU/ml at 48 weeks, 96 weeks, and 144 weeks. Participants in all groups will be stratified by whether they initiate treatment in Group A and B, and by the treatment regimens in Group C. The primary safety outcome is the change from baseline in the Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at 48 weeks, 96 weeks, and 144 weeks. The secondary outcomes including HBsAg loss, HBsAg seroconversion, HBeAg loss, HBeAg seroconversion, fibrosis regression and progression, and liver-related events, which will be measured at each follow-up visit. The follow-up time course of this study will be 3 years.

Conditions: Hepatitis B, Chronic
Being tested: ETV/TAF/TDF/TMF/IFN, ETV/TAF/TDF/TMF
Medical subject headings: Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ETV/TAF/TDF/TMF/IFNDrug
peginterferon alpha or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study
ETV/TAF/TDF/TMFDrug
peginterferon alpha or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study

Study groups in NCT05937178
Study group	Role	What they receive
Recommend to initiate treatment in 2022 Chinese Guideline, but not in 2019 Chinese Guideline		Untreated population who does not be recommended to initiate treatment in 2022 Chinese Guideline, but not in 2019 Chinese Guideline. The initate treatment is to receive a first-line nucleos(t)ide analogue, i.e., entecavir, tenofovir disoproxil, or tenofovir alafenamide, tenofovir amibufenamide Receives: Drug: ETV/TAF/TDF/TMF
Recommend to initiate treatment in 2019 and 2022 Chinese Guideline, but not in AASLD/EASL guidelines		Untreated population will receive a first-line nucleos(t)ide analogue , i.e., entecavir, tenofovir disoproxil, or tenofovir alafenamide, tenofovir amibufenamide, and the population should meet the conditions that are recommended to initiate treatment in 2019 and 2022 Chinese guideline, but not in AASLD/EASL guidelines Receives: Drug: ETV/TAF/TDF/TMF
Treatment experienced and with partial response		Treatment experienced population who has received a first-line nucleos(t)ide analogue(NA) as monotherapy at least 48 weeks, i.e., entecavir, tenofovir disoproxil, or tenofovir alafenamide, tenofovir amibufenamide, and has partial response to NA. They will continue the original therpay or plans to change the therapy (e.g. switch another first-line NA, add-on another first-line NA, switch another first-line NA and add-on peginterferon alpha) Receives: Drug: ETV/TAF/TDF/TMF/IFN

What is being measured

The primary outcome is the main question the study is designed to answer.

The proportion of patients with HBV DNA <20 IU/ml
The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at each follow-up time point, as determined by high-sensitivity PCR
Measured: Week 48
The proportion of patients with HBV DNA <20 IU/ml
The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at each follow-up time point, as determined by high-sensitivity PCR
Measured: Week 96
The proportion of patients with HBV DNA <20 IU/ml
The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at each follow-up time point, as determined by high-sensitivity PCR
Measured: Week 144
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at each follow-up time point
Measured: Baseline
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at each follow-up time point
Measured: Week 48
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at each follow-up time point
Measured: Week 96
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at each follow-up time point
Measured: Week 144

Secondary outcomes (7)

Proportion of participants with Normal Alanine Aminotransferase (ALT)
Proportion of participants with Normal Alanine Aminotransferase (ALT) at each follow-up time point
Measured: Week 48, Week 96 and Week 144
Proportion of participants with Hepatitis B s Antigen (HBsAg) Loss
Proportion of participants with Hepatitis B s Antigen (HBsAg) Loss at each follow-up time point
Measured: Week 48, Week 96 and Week 144
Proportion of participants with Hepatitis B s Antigen (HBeAg) Loss
Proportion of participants with Hepatitis B s Antigen (HBeAg) Loss at each follow-up time point
Measured: Week 48, Week 96 and Week 144
Proportion of participants with seroconversion to Hepatitis B s Antigen (HBsAg)
Proportion of participants with seroconversion to Hepatitis B s Antigen (HBsAg) at each follow-up time point
Measured: Week 48, Week 96 and Week 144
Proportion of participants with seroconversion to Hepatitis B e Antigen (HBeAg)
Proportion of participants with seroconversion to Hepatitis B e Antigen (HBeAg) at each follow-up time point
Measured: Week 48, Week 96 and Week 144
Proportion of participants with fibrosis regression and progression
Proportion of participants with fibrosis regression and progression at each follow-up time point
Measured: Week 48, Week 96 and Week 144
Rate of liver-related events
Rate of liver-related events (HCC, decompensation cirrhosis, death) at each follow-up time point
Measured: Week 48, Week 96 and Week 144

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Jan 202331 Jan 2029

First posted10 Jul 2023
Study start31 Jan 2023
Primary completion31 Jan 2029 (estimated)
Study completion31 Jan 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (15)Papers the sponsor has linked to this study.
Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 20,000 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05937178
Sponsor's protocol ID: REASON
Status last verified: Jul 2023
First submitted: 28 Jun 2023
Last updated: 10 Jul 2023
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):383-403. doi: 10.1016/S2468-1253(18)30056-6. Epub 2018 Mar 27.
PubMed 29599078
Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. [The guidelines of prevention and treatment for chronic hepatitis B (2019 version)]. Zhonghua Gan Zang Bing Za Zhi. 2019 Dec 20;27(12):938-961. doi: 10.3760/cma.j.issn.1007-3418.2019.12.007. Chinese.
PubMed 31941257
European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
PubMed 28427875
Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.
PubMed 29405329
Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015 Dec;64(12):1972-84. doi: 10.1136/gutjnl-2015-309809. Epub 2015 Jun 5.
PubMed 26048673
Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P, Ahn SH, Izumi N, Chuang WL, Bae H, Sharma M, Janssen HLA, Pan CQ, Celen MK, Furusyo N, Shalimar D, Yoon KT, Trinh H, Flaherty JF, Gaggar A, Lau AH, Cathcart AL, Lin L, Bhardwaj N, Suri V, Mani Subramanian G, Gane EJ, Buti M, Chan HLY; GS-US-320-0110; GS-US-320-0108 Investigators. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018 Apr;68(4):672-681. doi: 10.1016/j.jhep.2017.11.039. Epub 2018 Jan 17.
PubMed 29756595
Chinese Society of Infectious Disease Chinese Society of Hepatology; Chinese Medical Association. [The expert consensus on clinical cure (functional cure) of chronic hepatitis B]. Zhonghua Gan Zang Bing Za Zhi. 2019 Aug 20;27(8):594-603. doi: 10.3760/cma.j.issn.1007-3418.2019.08.003. Chinese.
PubMed 31594076
Zhang L, Fan ZF, Liu DW, Zhou MG, Wang ZQ, Li M. [Trend analysis on the disease burden related to cirrhosis and other chronic liver diseases caused by hepatitis B, in China, from 1990 to 2016]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 10;41(2):173-177. doi: 10.3760/cma.j.issn.0254-6450.2020.02.007. Chinese.
PubMed 32164125
Kim GA, Lim YS, An J, Lee D, Shim JH, Kim KM, Lee HC, Chung YH, Lee YS, Suh DJ. HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability. Gut. 2014 Aug;63(8):1325-32. doi: 10.1136/gutjnl-2013-305517. Epub 2013 Oct 25.
PubMed 24162593
Lim TH, Gane E, Moyes C, Borman B, Cunningham C. HBsAg loss in a New Zealand community study with 28-year follow-up: rates, predictors and long-term outcomes. Hepatol Int. 2016 Sep;10(5):829-37. doi: 10.1007/s12072-016-9709-6. Epub 2016 Mar 8.
PubMed 26957439
Sinn DH, Kim SE, Kim BK, Kim JH, Choi MS. The risk of hepatocellular carcinoma among chronic hepatitis B virus-infected patients outside current treatment criteria. J Viral Hepat. 2019 Dec;26(12):1465-1472. doi: 10.1111/jvh.13185. Epub 2019 Aug 13.
PubMed 31332935
ZHUANG H. Should chronic hepatitis B in the indeterminate phase be treated?[J]. J Clin Hepatol, 2021, 37(9): 2033-2036.
Chinese Society of Hepatology, Chinese Medical Association. [Expert opinion on expanding anti-HBV treatment for chronic hepatitis B]. Zhonghua Gan Zang Bing Za Zhi. 2022 Feb 20;30(2):131-136. doi: 10.3760/cma.j.cn501113-20220209-00060. Chinese.
PubMed 35359064
National Health and Family Planning Commission of the People's Republic of China. China Statistical Yearbook. Beijing: Peking Union Medical College Press, 2020.
Wang G, Duan Z. Guidelines for Prevention and Treatment of Chronic Hepatitis B. J Clin Transl Hepatol. 2021 Oct 28;9(5):769-791. doi: 10.14218/JCTH.2021.00209. Epub 2021 Sep 28.
PubMed 34722192

Interested in taking part?

Wenghong Zhang, MD

13801844344

zhangwenhong@fudan.edu.cn

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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Study at a glance

From the registry record, last updated by the sponsor on 10 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Real-world Study of Optimizing Nucleotide-analogues-based Treatment for Chronic Hepatitis B
ClinicalTrials.gov ID: NCT05937178
Acronym / sponsor ID: REASON
Conditions: Hepatitis B, Chronic
Study type: Observational
Recruitment status: Recruiting
Enrolment: 20,000 participants (estimated)
Lead sponsor: Huashan HospitalUniversity, hospital or other
Collaborators: The First Affiliated Hospital of Anhui Medical University, Anhui Provincial Hospital, Beijing YouAn Hospital, Peking University People's Hospital, Peking University First Hospital, Xiamen Hospital of Traditional Chinese Medicine, First Affiliated Hospital of Fujian Medical University, LanZhou University, Third Affiliated Hospital, Sun Yat-Sen University, First Affiliated Hospital of Guangxi Medical University, The Affiliated Hospital Of Guizhou Medical University, Hainan General Hospital, Hebei Medical University Third Hospital, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan Provincial People's Hospital, The Second Affiliated Hospital of Harbin Medical University, Tongji Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Renmin Hospital of Wuhan University, Central South University, Xiangya Hospital of Central South University, The First Hospital of Jilin University, the Second Hospital of Nangjing, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The First Affiliated Hospital with Nanjing Medical University, The Affiliated Hospital of Xuzhou Medical University, The First Affiliated Hospital of Nanchang University, Shengjing Hospital, Qingdao Sixth People's Hospital, Shandong Provincial Hospital, The Second Hospital of Shandong University, The First Affiliated Hospital of Shanxi Medical University, Tang-Du Hospital, First Affiliated Hospital Xi'an Jiaotong University, Ruijin Hospital, West China Hospital, Tianjin Second People's Hospital, First Affiliated Hospital of Xinjiang Medical University, The First People's Hospital of Yunnan, Shulan (Hangzhou) Hospital, Zhejiang University, Southwest Hospital, China, The Second Affiliated Hospital of Chongqing Medical University, Sichuan Provincial People's Hospital
Study start: 31 Jan 2023 (actual)
Primary completion: 31 Jan 2029 (estimated)
Study completion: 31 Jan 2029 (estimated)
First posted: 10 Jul 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To evaluate the benefits of initiating first-line nucleos(t)ide analogue in patients with chronic HBV infection who are recommended in the updated Chinese Guideline 2022, but not recommended in the Chinese Guideline 2019.
To evaluate the Chinese Guideline recommends initiation of treatment, but at least one foreign authoritative guideline (eg. AASLD, EASL) does not recommend the benefit of initiating first-line nucleos(t)ide analogue in patients with chronic HBV infection who initiate treatment.
To compare the treatment effect of different alternatives with patients who have partial response after treatment with first-line nucleos(t)ide analogues.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 3

Arm	Type	Receives
Recommend to initiate treatment in 2022 Chinese Guideline, but not in 2019 Chinese Guideline	–	Drug: ETV/TAF/TDF/TMFUntreated population who does not be recommended to initiate treatment in 2022 Chinese Guideline, but not in 2019 Chinese Guideline. The initate treatment is to receive a first-line nucleos(t)ide analogue, i.e., entecavir, tenofovir disoproxil, or tenofovir alafenamide, tenofovir amibufenamide
Recommend to initiate treatment in 2019 and 2022 Chinese Guideline, but not in AASLD/EASL guidelines	–	Drug: ETV/TAF/TDF/TMFUntreated population will receive a first-line nucleos(t)ide analogue , i.e., entecavir, tenofovir disoproxil, or tenofovir alafenamide, tenofovir amibufenamide, and the population should meet the conditions that are recommended to initiate treatment in 2019 and 2022 Chinese guideline, but not in AASLD/EASL guidelines
Treatment experienced and with partial response	–	Drug: ETV/TAF/TDF/TMF/IFNTreatment experienced population who has received a first-line nucleos(t)ide analogue(NA) as monotherapy at least 48 weeks, i.e., entecavir, tenofovir disoproxil, or tenofovir alafenamide, tenofovir amibufenamide, and has partial response to NA. They will continue the original therpay or plans to change the therapy (e.g. switch another first-line NA, add-on another first-line NA, switch another first-line NA and add-on peginterferon alpha)

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Patients with chronic hepatitis B will receive the first-line antiviral therapy

Key inclusion criteria (11 listed)

CHB defined as positive hepatitis B surface antigen at least 6 months, or HBV-related histological changes within 1 year if HBsAg positive less than 6 months.
Age between 18-80 years.
Patient who reads and signs informed consent.
Meet any conditions of the group listed below
Group A-naïve and meeting the conditions that are recommended to initiate treatment in 2022 Chinese Guideline, but not in 2019 Chinese Guideline (observe-plan to treat or control-plan to follow-up) :

Key exclusion criteria (3 listed)

Have poor compliance;
Received contraindicated concomitant drugs (subjects receiving prohibited drugs will need at least 30 days of washing out period) and known hypersensitivity reactions to the study drug, metabolites, or formulated excipients;
Any other clinical symptoms or previous treatment that the investigator considers that the individual subject is not suitable for this study or cannot comply with the administration requirements

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ETV/TAF/TDF/TMF/IFNpeginterferon alpha or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study	Drug	Treatment experienced and with partial response
ETV/TAF/TDF/TMFpeginterferon alpha or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study	Drug	Recommend to initiate treatment in 2019 and 2022 Chinese Guideline, but not in AASLD/EASL guidelines, Recommend to initiate treatment in 2022 Chinese Guideline, but not in 2019 Chinese Guideline

Primary outcome

The proportion of patients with HBV DNA <20 IU/ml
Time frame: Week 48
The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at each follow-up time point, as determined by high-sensitivity PCR
The proportion of patients with HBV DNA <20 IU/ml
Time frame: Week 96
The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at each follow-up time point, as determined by high-sensitivity PCR
The proportion of patients with HBV DNA <20 IU/ml
Time frame: Week 144
The primary efficacy endpoint was the proportion of patients with HBV DNA <20 IU/ml at each follow-up time point, as determined by high-sensitivity PCR
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
Time frame: Baseline
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at each follow-up time point
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
Time frame: Week 48
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at each follow-up time point
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
Time frame: Week 96
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at each follow-up time point
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
Time frame: Week 144
Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG) at each follow-up time point

7 secondary outcomes

Proportion of participants with Normal Alanine Aminotransferase (ALT)
Time frame: Week 48, Week 96 and Week 144
Proportion of participants with Hepatitis B s Antigen (HBsAg) Loss
Time frame: Week 48, Week 96 and Week 144
Proportion of participants with Hepatitis B s Antigen (HBeAg) Loss
Time frame: Week 48, Week 96 and Week 144
Proportion of participants with seroconversion to Hepatitis B s Antigen (HBsAg)
Time frame: Week 48, Week 96 and Week 144
Proportion of participants with seroconversion to Hepatitis B e Antigen (HBeAg)
Time frame: Week 48, Week 96 and Week 144
Proportion of participants with fibrosis regression and progression
Time frame: Week 48, Week 96 and Week 144
Rate of liver-related events
Time frame: Week 48, Week 96 and Week 144

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2023.
Background: PubMed 29599078Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):383-403. doi: 10.1016/S2468-1253(18)30056-6. Epub 2018 Mar 27.
Background: PubMed 31941257Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. [The guidelines of prevention and treatment for chronic hepatitis B (2019 version)]. Zhonghua Gan Zang Bing Za Zhi. 2019 Dec 20;27(12):938-961. doi: 10.3760/cma.j.issn.1007-3418.2019.12.007. Chinese.
Background: PubMed 28427875European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
Background: PubMed 29405329Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.
Background: PubMed 26048673Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015 Dec;64(12):1972-84. doi: 10.1136/gutjnl-2015-309809. Epub 2015 Jun 5.
Background: PubMed 29756595Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P, Ahn SH, Izumi N, Chuang WL, Bae H, Sharma M, Janssen HLA, Pan CQ, Celen MK, Furusyo N, Shalimar D, Yoon KT, Trinh H, Flaherty JF, Gaggar A, Lau AH, Cathcart AL, Lin L, Bhardwaj N, Suri V, Mani Subramanian G, Gane EJ, Buti M, Chan HLY; GS-US-320-0110; GS-US-320-0108 Investigators. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018 Apr;68(4):672-681. doi: 10.1016/j.jhep.2017.11.039. Epub 2018 Jan 17.
Background: PubMed 31594076Chinese Society of Infectious Disease Chinese Society of Hepatology; Chinese Medical Association. [The expert consensus on clinical cure (functional cure) of chronic hepatitis B]. Zhonghua Gan Zang Bing Za Zhi. 2019 Aug 20;27(8):594-603. doi: 10.3760/cma.j.issn.1007-3418.2019.08.003. Chinese.
Background: PubMed 32164125Zhang L, Fan ZF, Liu DW, Zhou MG, Wang ZQ, Li M. [Trend analysis on the disease burden related to cirrhosis and other chronic liver diseases caused by hepatitis B, in China, from 1990 to 2016]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020 Feb 10;41(2):173-177. doi: 10.3760/cma.j.issn.0254-6450.2020.02.007. Chinese.
Background: PubMed 24162593Kim GA, Lim YS, An J, Lee D, Shim JH, Kim KM, Lee HC, Chung YH, Lee YS, Suh DJ. HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability. Gut. 2014 Aug;63(8):1325-32. doi: 10.1136/gutjnl-2013-305517. Epub 2013 Oct 25.
Background: PubMed 26957439Lim TH, Gane E, Moyes C, Borman B, Cunningham C. HBsAg loss in a New Zealand community study with 28-year follow-up: rates, predictors and long-term outcomes. Hepatol Int. 2016 Sep;10(5):829-37. doi: 10.1007/s12072-016-9709-6. Epub 2016 Mar 8.
Background: PubMed 31332935Sinn DH, Kim SE, Kim BK, Kim JH, Choi MS. The risk of hepatocellular carcinoma among chronic hepatitis B virus-infected patients outside current treatment criteria. J Viral Hepat. 2019 Dec;26(12):1465-1472. doi: 10.1111/jvh.13185. Epub 2019 Aug 13.
BackgroundZHUANG H. Should chronic hepatitis B in the indeterminate phase be treated?[J]. J Clin Hepatol, 2021, 37(9): 2033-2036.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Wenghong Zhang, MD contact

13801844344

zhangwenhong@fudan.edu.cn

Wenghong Zhang, MD principal investigator

Huashan Hospital

Jiming Zhang, MD principal investigator

Huashan Hospital

Feng S, MD study chair

Huashan Hospital

44 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Hepatitis B, Chronic, run by Huashan Hospital at 44 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Wenghong Zhang, MD (13801844344, zhangwenhong@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of patients with HBV DNA <20 IU/ml (time frame: Week 48). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05937178, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2023.