Hepatitis B, ChronicNCT05376124
Clinical Characteristics, Natural Outcome and Treatment Optimization of Refractory
An observational study of Hepatitis B, Chronic and Virus Diseases, run by First Affiliated Hospital Xi'an Jiaotong University at 13 sites in China.
Trial summary
Refractory hepatitis B is to point to although standard application nucleoside (acid) analogue treatment undertakes primary treatment and two strengthen treatment, but existence is persistent viremia. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis B, Chronic, Virus Diseases
- What is being tested?
- original therapy and rescue therapy
- Type of treatment
- Pill or oral medicine
- How many people
- 110 participants
- Where
- 13 sitesChina
- Study dates
- 1 Jan 2022to 31 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with refractory hepatitis B in January 2022 to January 2023 of The First Affiliated Hospital of Xi 'an Jiaotong University、The Second Affiliated Hospital of Xi 'an Jiaotong University、 Xijing Hospital Air Force Medical University 、Tang-du Hospital 、Shaanxi Provincial People's Hospital Xi 'an Central Hospital、 Ankang Central Hospital 、Yan 'an University Affiliated Hospital、 Hanzhong 3201 Hospital Weinan Central Hospital 、The First Affiliated Hospital of Shandong Medical University、Wuhan Union Hospital、The First Affiliated Hospital of Zhengzhou University. All patients were required to sign written informed consent before enrollment
Who may be able to join
- (1) The diagnostic criteria of chronic hepatitis B: HBsAg and/or HBV DNA positive for more than 6 months; (2) Conforming to the definition of refractory hepatitis B (3) Aged between 18 and 70 (including 18 and 70); (4) Willing to accept treatment and sign informed consent.
Who cannot join
- (1) Pregnant women or lactating women; (2) with active HEPATITIS A, hepatitis C, and hepatitis D (in hospitals where conditions permit), hepatitis E and/or HIV infection; (3) Decompensated cirrhosis (Child-Pugh score 6); (4) Symptoms and signs of hepatocellular carcinoma, AFP\> Patients with 100ng/ml of AFP would be excluded, but patients whose AFP remained stable (increased by less than 10%) for more than 3 months prior to the trial could be enrolled in patients whose liver tumors were excluded by liver imaging if AFP\> 20ng/mL but 100ng/mL can be selected; (5) In addition to viral hepatitis, other history or evidence related to chronic liver disease (such as hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposure, thalassemia); (6) a history of serious mental illness, especially depression severe mental illness is defined as at least 3 months before the above treatment dose antidepressant or antipsychotic drug treatment of severe depression or psychosis, or there are any medical history: once for attempted suicide was hospitalized due to mental illness, or had a disability due to mental illness; (7) a history of severe seizures or current use of anticonvulsants; (8) a history of chronic lung disease related to functional limitations; (9) A history of severe heart disease (NYHA grade III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmia requiring continued treatment, unstable angina or other important cardiovascular disease); (10) patients who are participating in other trials or have been treated with the study drug in the 12 weeks prior to screening; (11) Patients with a history of allergy to ETV, TDF and TAF; In addition to the above exclusion criteria, patients who meet any of the contraindications in the experimental drug description; (12) Unable or unwilling to provide informed consent or comply with the requirements of the study.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
China13 sites, 13 recruiting
- Recruiting
Ankang Central Hospital
Ankang
Kui Li, 13571422201
- Recruiting
Hanzhong 3201 Hospital
Hanzhong
Yongmei Lin, 13109188835
- Recruiting
Qianfhan Hospital
Jinan
- Recruiting
Weinan Central Hospital
Weinan
Hongbin Li, 13468902958
- Recruiting
Wuhan Union Hospital
Wuhan
- Recruiting
Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an
Yingli He, 18991232863, heyingli2000@163.com
Nan Yang, 13572227780, shmily.1989.2008@stu.xjtu.edu.cn
- Recruiting
Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an
Fanpu Ji, 15319435860
- Recruiting
Shaanxi Provincial People's Hospital
Xi'an
- Recruiting
Tang-Du Hospital
Xi'an
Hong Du
- Recruiting
Xi'an Central Hospital
Xi'an
- Recruiting
Xijing hospital of air force Medical University
Xi'an
- Recruiting
Yan'an University Affiliated Hospital
Yan’an
- Recruiting
The First Affiliated Hospital of Zhengzhou University
Zhengzhou
About this study
Official title: Clinical Characteristics, Natural Outcome and Treatment Optimization of Refractory Hepatitis B: a Open Label, Prospective, Multi-center Cohort Study
Refractory hepatitis B is to point to although standard application nucleoside (acid) analogue treatment undertakes primary treatment and two strengthen treatment, but existence is persistent viremia. Currently, there is no consensus on salvage therapy for patients who remain virus-positive after a second round of antiviral therapy. This is the first multicenter, prospective, parallel controlled, open-label cohort study to compare the efficacy and safety of TDF/TAF combined with ETV1.0mg regimen versus continuation of the original regimen in the treatment of refractory hepatitis B.
Read the detailed description
Refractory sex hepatitis B is to point to although standard application nucleoside (acid) analogue treatment undertakes first treat and 2 strengthen treat cure, but existence is persistent viraemia. These patients have active liver inflammation and are at high risk for progression to cirrhosis or primary liver cancer due to persistent virus-positive symptoms. Therefore, it is of great significance to find an effective antiviral program for refractory hepatitis B to reduce the fatality rate of hepatitis B in China. At present, the guidelines recommend that patients with drug resistance to Entecavir (ETV) be treated with tenofovir fumarate (TDF) or propofol tenofovir fumarate (TAF), and clinical studies in China have confirmed that increased dosage of entecavir to 1.0mg can be used as the treatment of drug resistance to entecavir. TDF and TAF resistant patients can be treated with entecavir 0.5mg. However, currently there is no consensus on salvage treatment for patients who remain virus-positive after a second round of antiviral therapy. Previous studies have shown that TDF/TAF combined with ETV 1.0mg as a rescue regimen has no obvious adverse drug reactions. This is the first multicenter, prospective, parallel controlled, open-label cohort study to compare the efficacy and safety of TDF/TAF combined with ETV 1.0mg regimen versus continuation of the original regimen in the treatment of refractory hepatitis B. Meanwhile, long-term outcomes of refractory hepatitis B patients, such as survival, cirrhosis and primary liver cancer, were observed. In addition, the effects of refractory hepatitis B virus strain, host and other clinical characteristics on the antiviral efficacy of nucleoside (acid) analogue were compared with those of patients with initial treatment and secondary enhancement of nucleoside (acid) analogue response. The results of this study are expected to provide a new perspective for the treatment of refractory hepatitis B and provide direct evidence for the formulation of guidelines for the diagnosis and treatment of chronic hepatitis B in China and even internationally.
- Conditions
- Hepatitis B, Chronic, Virus Diseases
- Being tested
- original therapy, rescue therapy
- Keywords
- HBV, Refractory hepatitis B, Clinical characteristics, Natural outcome, nucleoside analog
- Medical subject headings
- Hepatitis B, Chronic, Virus Diseases, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
original therapyOther
- Patients on ETV 0.5mg/ day or TDF 300mg/ day or TAF 25mg/ day continued the original regimen (ETV 1.0mg/ day or TDF 300mg/ day or TAF 25mg/ day), Oral treatment lasted 48 weeks ②Patients who received TDF 300mg/ day plus ETV 0.5mg/ day on initial treatment continued with the original regimen (TDF 300mg/ day plus ETV 0.5mg/ day) and oral therapy for 48 weeks ③Patients who received TAF 25mg/ day plus ETV 0.5mg/ day as initial treatment continued the original regimen (TAF 25mg/ day plus ETV 0.5mg/ day) for 48 weeks of oral therapy
rescue therapyOther
TDF 300mg/ day +ETV 1.0mg/ day or TAF 25mg/ day +ETV 1.0mg/ day, oral treatment for 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| original therapy | ETV 0.5mg/ day or TDF 300mg/ day or TAF 25mg/ day continued the original regimen (ETV 1.0mg/ day or TDF 300mg/ day or TAF 25mg/ day), Oral treatment lasted 48 weeks ②TDF 300mg/ day plus ETV 0.5mg/ day on initial treatment continued with the original regimen (TDF 300mg/ day plus ETV 0.5mg/ day) and oral therapy for 48 weeks ③TAF 25mg/ day plus ETV 0.5mg/ day as initial treatment continued the original regimen (TAF 25mg/ day plus ETV 0.5mg/ day) for 48 weeks of oral therapy Receives: Other: original therapy | |
| rescue therapy | TDF 300mg/ day +ETV 1.0mg/ day or TAF 25mg/ day +ETV 1.0mg/ day, oral treatment for 48 weeks. Receives: Other: rescue therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Negative HBV-DNA conversion
Negative HBV-DNA conversion at 48 weeks of treatment
Measured: 48weeks
Liver hardness measurement
3-year liver hardness measurement (LSM value)
Measured: 3 years
Hepatocellular carcinoma
Incidence and survival of hepatocellular carcinoma.
Measured: 3 years
Secondary outcomes (4)
virology indicators
virology indicators: quantitative hbv-dna;
Measured: 48weeks
Biochemical indexes
Biochemical indexes: ALT level;
Measured: 3 years
Immunological indicators
Immunological indicators: HBsAg level and HBsAg disappearance HBeAg serological conversion;
Measured: 3 years
Drug-related adverse reactions
Drug-related adverse reactions
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2022
- Study start1 Jan 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital Xi'an Jiaotong UniversityThe sponsor's other registered studies.
- 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
- 110 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yingren Zhao, Principal investigator, Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05376124
- Sponsor's protocol ID
- XJTU1AF2021CRF-006
- Status last verified
- Oct 2022
- First submitted
- 11 May 2022
- Last updated
- 3 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Characteristics, Natural Outcome and Treatment Optimization of Refractory Hepatitis B: a Open Label, Prospective, Multi-center Cohort Study
- ClinicalTrials.gov ID
- NCT05376124
- Acronym / sponsor ID
- XJTU1AF2021CRF-006
- Conditions
- Hepatitis B, Chronic, Virus Diseases
- Keywords
- HBV, Refractory hepatitis B, Clinical characteristics, Natural outcome, nucleoside analog
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- First Affiliated Hospital Xi'an Jiaotong UniversityUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 17 May 2022 (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.
Refractory hepatitis B is to point to although standard application nucleoside (acid) analogue treatment undertakes primary treatment and two strengthen treatment, but existence is persistent viremia. Currently, there is no consensus on salvage therapy for patients who remain virus-positive after a second round of antiviral therapy. This is the first multicenter, prospective, parallel controlled, open-label cohort study to compare the efficacy and safety of TDF/TAF combined with ETV1.0mg regimen versus continuation of the original regimen in the treatment of refractory hepatitis B.
Detailed description
Refractory sex hepatitis B is to point to although standard application nucleoside (acid) analogue treatment undertakes first treat and 2 strengthen treat cure, but existence is persistent viraemia. These patients have active liver inflammation and are at high risk for progression to cirrhosis or primary liver cancer due to persistent virus-positive symptoms. Therefore, it is of great significance to find an effective antiviral program for refractory hepatitis B to reduce the fatality rate of hepatitis B in China. At present, the guidelines recommend that patients with drug resistance to Entecavir (ETV) be treated with tenofovir fumarate (TDF) or propofol tenofovir fumarate (TAF), and clinical studies in China have confirmed that increased dosage of entecavir to 1.0mg can be used as the treatment of drug resistance to entecavir. TDF and TAF resistant patients can be treated with entecavir 0.5mg. However, currently there is no consensus on salvage treatment for patients who remain virus-positive after a second round of antiviral therapy. Previous studies have shown that TDF/TAF combined with ETV 1.0mg as a rescue regimen has no obvious adverse drug reactions. This is the first multicenter, prospective, parallel controlled, open-label cohort study to compare the efficacy and safety of TDF/TAF combined with ETV 1.0mg regimen versus continuation of the original regimen in the treatment of refractory hepatitis B. Meanwhile, long-term outcomes of refractory hepatitis B patients, such as survival, cirrhosis and primary liver cancer, were observed. In addition, the effects of refractory hepatitis B virus strain, host and other clinical characteristics on the antiviral efficacy of nucleoside (acid) analogue were compared with those of patients with initial treatment and secondary enhancement of nucleoside (acid) analogue response. The results of this study are expected to provide a new perspective for the treatment of refractory hepatitis B and provide direct evidence for the formulation of guidelines for the diagnosis and treatment of chronic hepatitis B in China and even internationally.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| original therapy | – | Other: original therapyETV 0.5mg/ day or TDF 300mg/ day or TAF 25mg/ day continued the original regimen (ETV 1.0mg/ day or TDF 300mg/ day or TAF 25mg/ day), Oral treatment lasted 48 weeks ②TDF 300mg/ day plus ETV 0.5mg/ day on initial treatment continued with the original regimen (TDF 300mg/ day plus ETV 0.5mg/ day) and oral therapy for 48 weeks ③TAF 25mg/ day plus ETV 0.5mg/ day as initial treatment continued the original regimen (TAF 25mg/ day plus ETV 0.5mg/ day) for 48 weeks of oral therapy |
| rescue therapy | – | Other: rescue therapyTDF 300mg/ day +ETV 1.0mg/ day or TAF 25mg/ day +ETV 1.0mg/ day, oral treatment for 48 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with refractory hepatitis B in January 2022 to January 2023 of The First Affiliated Hospital of Xi 'an Jiaotong University、The Second Affiliated Hospital of Xi 'an Jiaotong University、 Xijing Hospital Air Force Medical University 、Tang-du Hospital 、Shaanxi Provincial People's Hospital Xi 'an Central Hospital、 Ankang Central Hospital 、Yan 'an University Affiliated Hospital、 Hanzhong 3201 Hospital Weinan Central Hospital 、The First Affiliated Hospital of Shandong Medical University、Wuhan Union Hospital、The First Affiliated Hospital of Zhengzhou University. All patients were required to sign written informed consent before enrollment
Key inclusion criteria (1 listed)
- (1) The diagnostic criteria of chronic hepatitis B: HBsAg and/or HBV DNA positive for more than 6 months; (2) Conforming to the definition of refractory hepatitis B (3) Aged between 18 and 70 (including 18 and 70); (4) Willing to accept treatment and sign informed consent.
Key exclusion criteria (1 listed)
- (1) Pregnant women or lactating women; (2) with active HEPATITIS A, hepatitis C, and hepatitis D (in hospitals where conditions permit), hepatitis E and/or HIV infection; (3) Decompensated cirrhosis (Child-Pugh score 6); (4) Symptoms and signs of hepatocellular carcinoma, AFP\> Patients with 100ng/ml of AFP would be excluded, but patients whose AFP remained stable (increased by less than 10%) for more than 3 months prior to the trial could be enrolled in patients whose liver tumors were excluded by liver imaging if AFP\> 20ng/mL but 100ng/mL can be selected; (5) In addition to viral hepatitis, other history or evidence related to chronic liver disease (such as hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposure, thalassemia); (6) a history of serious mental illness, especially depression severe mental illness is defined as at least 3 months before the above treatment dose antidepressant or antipsychotic drug treatment of severe depression or psychosis, or there are any medical history: once for attempted suicide was hospitalized due to mental illness, or had a disability due to mental illness; (7) a history of severe seizures or current use of anticonvulsants; (8) a history of chronic lung disease related to functional limitations; (9) A history of severe heart disease (NYHA grade III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmia requiring continued treatment, unstable angina or other important cardiovascular disease); (10) patients who are participating in other trials or have been treated with the study drug in the 12 weeks prior to screening; (11) Patients with a history of allergy to ETV, TDF and TAF; In addition to the above exclusion criteria, patients who meet any of the contraindications in the experimental drug description; (12) Unable or unwilling to provide informed consent or comply with the requirements of the study.
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 |
|---|---|---|
| original therapy* Patients on ETV 0.5mg/ day or TDF 300mg/ day or TAF 25mg/ day continued the original regimen (ETV 1.0mg/ day or TDF 300mg/ day or TAF 25mg/ day), Oral treatment lasted 48 weeks ②Patients who received TDF 300mg/ day plus ETV 0.5mg/ day on initial treatment continued with the original regimen (TDF 300mg/ day plus ETV 0.5mg/ day) and oral therapy for 48 weeks ③Patients who received TAF 25mg/ day plus ETV 0.5mg/ day as initial treatment continued the original regimen (TAF 25mg/ day plus ETV 0.5mg/ day) for 48 weeks of oral therapy | Other | original therapy |
| rescue therapyTDF 300mg/ day +ETV 1.0mg/ day or TAF 25mg/ day +ETV 1.0mg/ day, oral treatment for 48 weeks. | Other | rescue therapy |
Primary outcome
Negative HBV-DNA conversion
Time frame: 48weeks
Negative HBV-DNA conversion at 48 weeks of treatment
Liver hardness measurement
Time frame: 3 years
3-year liver hardness measurement (LSM value)
Hepatocellular carcinoma
Time frame: 3 years
Incidence and survival of hepatocellular carcinoma.
4 secondary outcomes
virology indicators
Time frame: 48weeks
Biochemical indexes
Time frame: 3 years
Immunological indicators
Time frame: 3 years
Drug-related adverse reactions
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2023.
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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. This study is not recruiting at the moment.
Yingren Zhao principal investigator
Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University
13 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 and Virus Diseases, run by First Affiliated Hospital Xi'an Jiaotong University at 13 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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 3 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yingren Zhao (18691232863, zhaoyingren@sohu.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Negative HBV-DNA conversion (time frame: 48weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Feb 2023.