Real-world Study Optimizing Nucleotide-analogues

July 7, 2023 updated by: Wen-hong Zhang, Huashan Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

20000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Shanghai, China, 200040
    • Anhui
      • Hefei, Anhui, China, 230000
        • Not yet recruiting
        • Anhui Provincial Hospital
        • Contact:
      • Hefei, Anhui, China, 230000
        • Not yet recruiting
        • The First Affiliated Hospital of Anhui Medical University
        • Contact:
    • Beijing
      • Beijing, Beijing, China, 100000
        • Recruiting
        • Peking University First Hospital
        • Contact:
      • Beijing, Beijing, China, 100000
        • Not yet recruiting
        • Peking University People's Hospital
        • Contact:
      • Beijing, Beijing, China, 100000
        • Not yet recruiting
        • Beijing YouAn Hospita
        • Contact:
    • Chongqing
      • Chongqing, Chongqing, China, 400000
        • Not yet recruiting
        • The Second Affiliated Hospital of Chongqing Medical University
        • Contact:
      • Chongqing, Chongqing, China, 400000
        • Not yet recruiting
        • The Southwest Hospital of AMU
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China, 350000
        • Not yet recruiting
        • First Affiliated Hospital of Fujian Medical University
        • Contact:
      • Xiamen, Fujian, China, 361000
        • Not yet recruiting
        • Xiamen Hospital of Traditional Chinese Medicine
        • Contact:
    • Gansu
      • Lanzhou, Gansu, China, 730000
        • Not yet recruiting
        • The First Hospital of Lanzhou University
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China, 530000
        • Not yet recruiting
        • First Affiliated Hospital of Guangxi Medical University
        • Contact:
    • Guizhou
      • Guiyang, Guizhou, China, 55000
        • Not yet recruiting
        • The Affiliated Hospital of Guizhou Medical University
        • Contact:
    • Ha'erbin
      • Ha'erbin, Ha'erbin, China, 150000
        • Not yet recruiting
        • The Second Affiliated Hospital of Harbin Medical University
        • Contact:
    • Hainan
      • Haikou, Hainan, China, 570100
        • Not yet recruiting
        • Hainan General Hospital
        • Contact:
    • Hebei
      • Shijiazhuang, Hebei, China, 050000
        • Not yet recruiting
        • The Third Hospital of Hebei Medical University
        • Contact:
    • Henan
      • Zhengzhou, Henan, China, 450000
        • Not yet recruiting
        • Henan Provincial People's Hospital
        • Contact:
      • Zhengzhou, Henan, China, 450000
        • Not yet recruiting
        • The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
        • Contact:
    • Hubei
      • Wuhan, Hubei, China, 430000
        • Not yet recruiting
        • Tongji Hospital
        • Contact:
      • Wuhan, Hubei, China, 430000
        • Not yet recruiting
        • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
      • Wuhan, Hubei, China, 430000
        • Not yet recruiting
        • Renmin Hospital of Wuhan University
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 430100
        • Not yet recruiting
        • The Second Xiangya Hospital of Central South University
        • Contact:
      • Changsha, Hunan, China, 430100
        • Not yet recruiting
        • Xiangya Hospital Central South University
        • Contact:
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Not yet recruiting
        • Jiangsu Province Hospital
        • Contact:
      • Nanjing, Jiangsu, China, 210000
        • Not yet recruiting
        • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
        • Contact:
      • Nanjing, Jiangsu, China, 210000
        • Not yet recruiting
        • the Second Hospital of Nangjing
        • Contact:
      • Xuzhou, Jiangsu, China, 221000
        • Recruiting
        • The Affiliated Hospital of Xuzhou Medical University
        • Contact:
    • Jiangxi
      • Nanchang, Jiangxi, China, 330000
        • Not yet recruiting
        • The First Affiliated Hospital of Nanchang University
        • Contact:
    • Jilin
      • Chang chun, Jilin, China, 130000
        • Not yet recruiting
        • The First Bethune Hospital of Jilin University
        • Contact:
    • Liaoning
      • Shenyang, Liaoning, China, 110000
        • Not yet recruiting
        • Shengjing Hospital of China Medical University
        • Contact:
    • Shaanxi
      • Xi'an, Shaanxi, China, 710000
        • Not yet recruiting
        • Tangdu Hospital, The Fourth Military Medical University
        • Contact:
      • Xi'an, Shaanxi, China, 710000
        • Not yet recruiting
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250000
        • Not yet recruiting
        • Shandong Provincial Hospital Affiliated to Shandong First Medical University
        • Contact:
      • Jinan, Shandong, China, 250000
        • Not yet recruiting
        • The Second Hospital of Shandong University
        • Contact:
          • Tao Li, Dr
          • Phone Number: 17660080982
      • Qingdao, Shandong, China, 266000
        • Not yet recruiting
        • No. 6 People's Hospital of Qingdao
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China, 200000
        • Not yet recruiting
        • Ruijin Hospital
        • Contact:
    • Shanxi
      • Taiyuan, Shanxi, China, 030000
        • Not yet recruiting
        • First Hospital of Shanxi Medical University
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • Not yet recruiting
        • West China Hospital of Sichuan University
        • Contact:
      • Chengdu, Sichuan, China, 610000
        • Not yet recruiting
        • Sichuan Provincial People's Hospital
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300000
        • Not yet recruiting
        • Tianjin Second People's Hospital
        • Contact:
    • Xiamen
      • Meizhou, Xiamen, China, 514000
        • Not yet recruiting
        • Third Affiliated Hospital, Sun Yat-Sen University
        • Contact:
    • Xinjiang Uygur Autonomous Region
      • Ürümqi, Xinjiang Uygur Autonomous Region, China, 830000
        • Not yet recruiting
        • Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine
        • Contact:
    • Yunnan
      • Kunming, Yunnan, China, 650000
        • Not yet recruiting
        • First People's Hospital of Yunnan Province
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310000
        • Not yet recruiting
        • Shulan (Hangzhou) Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
Drug: ETV/TAF/TDF/TMF
peginterferon alpha or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study
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
Drug: ETV/TAF/TDF/TMF
peginterferon alpha or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study
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)
Drug: ETV/TAF/TDF/TMF/IFN
peginterferon alpha or nucleos(t)ide alone are decided by patients' doctors according to their conditions, instead of extra interventions brought by the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Week 48
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
Week 96
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
Week 144
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
Baseline
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
Week 48
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
Week 96
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
Week 144

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Huashan Hospital

Collaborators

The First Affiliated Hospital with Nanjing Medical University
Peking University First Hospital
The First Affiliated Hospital of Anhui Medical University
The First Affiliated Hospital of Nanchang University
Xiangya Hospital of Central South University
LanZhou University
Peking University People's Hospital
Beijing YouAn Hospital
Southwest Hospital, China
West China Hospital
Tongji Hospital
First Affiliated Hospital of Fujian Medical University
Shengjing Hospital
First Affiliated Hospital Xi'an Jiaotong University
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Ruijin Hospital
The First Hospital of Jilin University
Henan Provincial People's Hospital
Third Affiliated Hospital, Sun Yat-Sen University
Wuhan Union Hospital, China
Renmin Hospital of Wuhan University
Central South University
The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
Zhejiang University
The Second Affiliated Hospital of Chongqing Medical University
The Affiliated Hospital Of Guizhou Medical University
Tang-Du Hospital
Hainan General Hospital
The Second Hospital of Shandong University
The Second Affiliated Hospital of Harbin Medical University
The First Affiliated Hospital of Shanxi Medical University
First Affiliated Hospital of Xinjiang Medical University
Hebei Medical University Third Hospital
Shandong Provincial Hospital Affiliated to Shandong First Medical University
Sichuan Provincial People's Hospital
The Affiliated Hospital of Xuzhou Medical University
Anhui Provincial Hospital
First Affiliated Hospital of Guangxi Medical University
The First People's Hospital of Yunnan
Tianjin Second People's Hospital
Shulan (Hangzhou) Hospital
Xiamen Hospital of Traditional Chinese Medicine
Qingdao Sixth People's Hospital
the Second Hospital of Nangjing

Investigators

  • Principal Investigator: Jiming Zhang, MD, Huashan Hospital
  • Study Director: Qiran Zhang, MD, Huashan Hospital
  • Principal Investigator: Wenghong Zhang, MD, Huashan Hospital
  • Study Chair: Feng S, MD, Huashan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 31, 2023

Primary Completion (Estimated)

January 31, 2029

Study Completion (Estimated)

January 31, 2029

Study Registration Dates

First Submitted

June 28, 2023

First Submitted That Met QC Criteria

July 7, 2023

First Posted (Actual)

July 10, 2023

Study Record Updates

Last Update Posted (Actual)

July 10, 2023

Last Update Submitted That Met QC Criteria

July 7, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REASON

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatitis B, Chronic

Clinical Trials on ETV/TAF/TDF/TMF

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Spain

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe