Real-world Study Optimizing Nucleotide-analogues

NCT05937178 | Recruiting

• 1 other identifier: REASON
• Study Type: observational
• Target: 20,000
• Locations: 1 country
• Sites: 44

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. 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. 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. 3.To compare the treatment effect of different alternatives with patients who have partial response after treatment with first-line nucleos(t)ide analogues.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (7)

• 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

  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

  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

  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

  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

  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

  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

  Week 144

Secondary Outcomes (7)

• Proportion of participants with Normal Alanine Aminotransferase (ALT)

  Week 48, Week 96 and Week 144

• Proportion of participants with Hepatitis B s Antigen (HBsAg) Loss

  Week 48, Week 96 and Week 144

• Proportion of participants with Hepatitis B s Antigen (HBeAg) Loss

  Week 48, Week 96 and Week 144

• Proportion of participants with seroconversion to Hepatitis B s Antigen (HBsAg)

  Week 48, Week 96 and Week 144

• Proportion of participants with seroconversion to Hepatitis B e Antigen (HBeAg)

  Week 48, Week 96 and Week 144

Study Arms (3)

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

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

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

Interventions

ETV/TAF/TDF/TMF/IFN DRUG

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

ETV/TAF/TDF/TMF DRUG

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; Recommend to initiate treatment in 2022 Chinese Guideline, but not in 2019 Chinese Guideline

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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
• 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) :
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (44)

Anhui Provincial Hospital

Hefei, Anhui, 230000, China

NOT YET RECRUITING

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230000, China

NOT YET RECRUITING

Beijing YouAn Hospita

Beijing, Beijing Municipality, 100000, China

NOT YET RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

Peking University People's Hospital

Beijing, Beijing Municipality, 100000, China

NOT YET RECRUITING

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400000, China

NOT YET RECRUITING

the Southwest Hospital of AMU

Chongqing, Chongqing Municipality, 400000, China

NOT YET RECRUITING

First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350000, China

NOT YET RECRUITING

Xiamen Hospital of Traditional Chinese Medicine

Xiamen, Fujian, 361000, China

NOT YET RECRUITING

the First Hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

NOT YET RECRUITING

First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530000, China

NOT YET RECRUITING

The Affiliated Hospital Of Guizhou Medical University

Guiyang, Guizhou, 55000, China

NOT YET RECRUITING

The Second Affiliated Hospital of Harbin Medical University

Ha’erbin, Ha'erbin, 150000, China

NOT YET RECRUITING

Hainan General Hospital

Haikou, Hainan, 570100, China

NOT YET RECRUITING

the Third Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

NOT YET RECRUITING

Henan Provincial People's Hospital

Zhengzhou, Henan, 450000, China

NOT YET RECRUITING

The First Affiliated Hospital of Henan University of Traditional Chinese Medicine

Zhengzhou, Henan, 450000, China

NOT YET RECRUITING

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430000, China

NOT YET RECRUITING

Tongji Hospital

Wuhan, Hubei, 430000, China

NOT YET RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

NOT YET RECRUITING

the Second Xiangya Hospital of Central South University

Changsha, Hunan, 430100, China

NOT YET RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, 430100, China

NOT YET RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210000, China

NOT YET RECRUITING

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210000, China

NOT YET RECRUITING

the Second Hospital of Nangjing

Nanjing, Jiangsu, 210000, China

NOT YET RECRUITING

the Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

RECRUITING

the First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330000, China

NOT YET RECRUITING

the First Bethune Hospital Of Jilin University

Changchun, Jilin, 130000, China

NOT YET RECRUITING

Shengjing Hospital of China Medical University

Shenyang, Liaoning, 110000, China

NOT YET RECRUITING

Tangdu Hospital, The Fourth Military Medical University

Xi'an, Shaanxi, 710000, China

NOT YET RECRUITING

the First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

NOT YET RECRUITING

Shandong Provincial Hospital Affiliated to Shandong First Medical University

Jinan, Shandong, 250000, China

NOT YET RECRUITING

The Second Hospital of Shandong University

Jinan, Shandong, 250000, China

NOT YET RECRUITING

No. 6 People's Hospital of Qingdao

Qingdao, Shandong, 266000, China

NOT YET RECRUITING

Ruijin Hospital

Shanghai, Shanghai Municipality, 200000, China

NOT YET RECRUITING

First Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030000, China

NOT YET RECRUITING

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610000, China

NOT YET RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610000, China

NOT YET RECRUITING

Tianjin Second People's Hospital

Tianjin, Tianjin Municipality, 300000, China

NOT YET RECRUITING

Third Affiliated Hospital, Sun Yat-Sen University

Meizhou, Xiamen, 514000, China

NOT YET RECRUITING

Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine

Ürümqi, Xinjiang Uygur Autonomous Region, 830000, China

NOT YET RECRUITING

First People's Hospital of Yunnan Province

Kunming, Yunnan, 650000, China

NOT YET RECRUITING

Shulan (Hangzhou) Hospital

Hangzhou, Zhejiang, 310000, China

NOT YET RECRUITING

Huashan Hospital

Shanghai, 200040, China

RECRUITING

Related Publications (15)

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• 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.

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  PMID: 35359064 BACKGROUND

• National Health and Family Planning Commission of the People's Republic of China. China Statistical Yearbook. Beijing: Peking Union Medical College Press, 2020.

  BACKGROUND

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MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wenghong Zhang, MD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

• Jiming Zhang, MD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

• Feng S, MD

  Huashan Hospital

  STUDY CHAIR

• Qiran Zhang, MD

  Huashan Hospital

  STUDY DIRECTOR

Central Study Contacts

Wenghong Zhang, MD

CONTACT

13801844344; zhangwenhong@fudan.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Division of Infectious Diseases

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 10, 2023
• Study Start: January 31, 2023
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2029
• Last Updated: July 10, 2023

Record last verified: 2023-07

Locations

CN (44)