Clinical trial NCT05376124: Clinical Characteristics, Natural Outcome and Treatment Optimization of Refractory
Official title: Clinical Characteristics, Natural Outcome and Treatment Optimization of Refractory Hepatitis B: a Open Label, Prospective, Multi-center Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatitis B, Chronic
Virus Diseases
Keywords: HBV
Refractory hepatitis B
Clinical characteristics
Natural outcome
nucleoside analog
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2022-05-17
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* (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.

Exclusion Criteria:

* (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\&gt; 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\&gt; 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.

Primary outcomes:
measure: Negative HBV-DNA conversion
timeFrame: 48weeks
measure: Liver hardness measurement
timeFrame: 3 years
measure: Hepatocellular carcinoma
timeFrame: 3 years
Secondary outcomes:
measure: virology indicators
timeFrame: 48weeks
measure: Biochemical indexes
timeFrame: 3 years
measure: Immunological indicators
timeFrame: 3 years
measure: Drug-related adverse reactions
timeFrame: 3 years
Other outcomes:
measure: Strain mutation indicators
timeFrame: 1year,2years and 3years
Locations:
city: Ankang
country: China
facility: Ankang Central Hospital
city: Hanzhong
country: China
facility: Hanzhong 3201 Hospital
city: Jinan
country: China
facility: Qianfhan Hospital
city: Weinan
country: China
facility: Weinan Central Hospital
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Xi'an
country: China
facility: Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University
city: Xi'an
country: China
facility: Second Affiliated Hospital of Xi'an Jiaotong University
city: Xi'an
country: China
facility: Shaanxi Provincial People's Hospital
city: Xi'an
country: China
facility: Tang-Du Hospital
city: Xi'an
country: China
facility: Xi'an Central Hospital
city: Xi'an
country: China
facility: Xijing hospital of air force Medical University
city: Yan'an
country: China
facility: Yan'an University Affiliated Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University
name: Yingren Zhao
role: PRINCIPAL_INVESTIGATOR
References: