Clinical trial NCT05937178: Real-world Study Optimizing Nucleotide-analogues
Official title: A Real-world Study of Optimizing Nucleotide-analogues-based Treatment for Chronic Hepatitis B
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatitis B, Chronic
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Anhui Medical University
name: Anhui Provincial Hospital
name: Beijing YouAn Hospital
name: Peking University People's Hospital
name: Peking University First Hospital
name: Xiamen Hospital of Traditional Chinese Medicine
name: First Affiliated Hospital of Fujian Medical University
name: LanZhou University
name: Third Affiliated Hospital, Sun Yat-Sen University
name: First Affiliated Hospital of Guangxi Medical University
name: The Affiliated Hospital Of Guizhou Medical University
name: Hainan General Hospital
name: Hebei Medical University Third Hospital
name: The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
name: Henan Provincial People's Hospital
name: The Second Affiliated Hospital of Harbin Medical University
name: Tongji Hospital
name: Wuhan Union Hospital, China
name: Renmin Hospital of Wuhan University
name: Central South University
name: Xiangya Hospital of Central South University
name: The First Hospital of Jilin University
name: the Second Hospital of Nangjing
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: The First Affiliated Hospital with Nanjing Medical University
name: The Affiliated Hospital of Xuzhou Medical University
name: The First Affiliated Hospital of Nanchang University
name: Shengjing Hospital
name: Qingdao Sixth People's Hospital
name: Shandong Provincial Hospital
name: The Second Hospital of Shandong University
name: The First Affiliated Hospital of Shanxi Medical University
name: Tang-Du Hospital
name: First Affiliated Hospital Xi'an Jiaotong University
name: Ruijin Hospital
name: West China Hospital
name: Tianjin Second People's Hospital
name: First Affiliated Hospital of Xinjiang Medical University
name: The First People's Hospital of Yunnan
name: Shulan (Hangzhou) Hospital
name: Zhejiang University
name: Southwest Hospital, China
name: The Second Affiliated Hospital of Chongqing Medical University
name: Sichuan Provincial People's Hospital
First posted: 2023-07-10
Enrollment: 20000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with chronic hepatitis B will receive the first-line antiviral therapy

Brief 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. 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.
2. 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.
3. 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: 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.

Eligibility criteria: Inclusion Criteria:

* 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) :

A. 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

1. Age\>30 years, and have a family history of cirrhosis or HCC, TE indicates no significant fibrosis;
2. Family history of cirrhosis or HCC, and ≤30 years, TE indicates no significant fibrosis;
3. 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) :

A. 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: The proportion of patients with HBV DNA <20 IU/ml
timeFrame: Week 48
measure: The proportion of patients with HBV DNA <20 IU/ml
timeFrame: Week 96
measure: The proportion of patients with HBV DNA <20 IU/ml
timeFrame: Week 144
measure: Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
timeFrame: Baseline
measure: Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
timeFrame: Week 48
measure: Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
timeFrame: Week 96
measure: Change from baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFR-CG)
timeFrame: Week 144
Secondary outcomes:
measure: Proportion of participants with Normal Alanine Aminotransferase (ALT)
timeFrame: Week 48, Week 96 and Week 144
measure: Proportion of participants with Hepatitis B s Antigen (HBsAg) Loss
timeFrame: Week 48, Week 96 and Week 144
measure: Proportion of participants with Hepatitis B s Antigen (HBeAg) Loss
timeFrame: Week 48, Week 96 and Week 144
measure: Proportion of participants with seroconversion to Hepatitis B s Antigen (HBsAg)
timeFrame: Week 48, Week 96 and Week 144
measure: Proportion of participants with seroconversion to Hepatitis B e Antigen (HBeAg)
timeFrame: Week 48, Week 96 and Week 144
measure: Proportion of participants with fibrosis regression and progression
timeFrame: Week 48, Week 96 and Week 144
measure: Rate of liver-related events
timeFrame: Week 48, Week 96 and Week 144
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing YouAn Hospita
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: the Southwest Hospital of AMU
state: Chongqing
city: Fuzhou
country: China
facility: First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Xiamen
country: China
facility: Xiamen Hospital of Traditional Chinese Medicine
state: Fujian
city: Lanzhou
country: China
facility: the First Hospital of Lanzhou University
state: Gansu
city: Nanning
country: China
facility: First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Hospital Of Guizhou Medical University
state: Guizhou
city: Ha'erbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Ha'erbin
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Shijiazhuang
country: China
facility: the Third Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: the Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
city: Nanjing
country: China
facility: the Second Hospital of Nangjing
state: Jiangsu
city: Xuzhou
country: China
facility: the Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: the First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Chang chun
country: China
facility: the First Bethune Hospital Of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Xi'an
country: China
facility: Tangdu Hospital, The Fourth Military Medical University
state: Shaanxi
city: Xi'an
country: China
facility: the First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Shandong Provincial Hospital Affiliated to Shandong First Medical University
state: Shandong
city: Jinan
country: China
facility: The Second Hospital of Shandong University
state: Shandong
city: Qingdao
country: China
facility: No. 6 People's Hospital of Qingdao
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Second People's Hospital
state: Tianjin
city: Meizhou
country: China
facility: Third Affiliated Hospital, Sun Yat-Sen University
state: Xiamen
city: Ürümqi
country: China
facility: Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine
state: Xinjiang Uygur Autonomous Region
city: Kunming
country: China
facility: First People's Hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: Shulan (Hangzhou) Hospital
state: Zhejiang
city: Shanghai
country: China
facility: Huashan Hospital
Study officials:
affiliation: Huashan Hospital
name: Wenghong Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Jiming Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Feng S, MD
role: STUDY_CHAIR
affiliation: Huashan Hospital
name: Qiran Zhang, MD
role: STUDY_DIRECTOR
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