The Study on Clinical Outcome and Treatment Optimization of Chronic Hepatitis B Patients With Hypoviremia

May 9, 2022 updated by: Yao Xie, Beijing Ditan Hospital

The Clinical Outcomes of Optimize Treatment of Chronic Hepatitis B Patients With Low-level Viremia Undergoing Nucleoside Treatment

Chronic hepatitis B seriously endangers the health of our people, especially the occurrence of HCC, which brings huge economic burden and life threat to our people. 84% - 92% of HCC in China is related to chronic HBV infection. How to further reduce the risk of liver cancer is an urgent problem to be solved in clinical research and an important direction. Although NAs treatment can make patients achieve the negative transformation of virus, it can not effectively reduce the level of virus antigen, and it also lacks the ability to improve the immune clearance of virus. As a result, the incidence of liver cancer in patients with long-term NA treatment is still 4.5% - 10.5%, and the incidence of HCC in patients with hypoviremia in Na treatment is higher. In current clinical practice, nearly 1 / 3 of patients treated with NAs can not reach the detection line of highly sensitive reagent. It is an important measure to make the patients with hypoviremia and inactive low virus replication treated by NAs below the detection line of highly sensitive reagent and further reduce the risk of HCC. However, it is still not enough to minimize the risk of HCC to achieve a complete viral response only through NA treatment. The long-term follow-up showed that the incidence of HBsAg disappeared by only 2.0% - 0.0% regardless of the long-term treatment of HBsAg. Therefore, the most important measure to minimize the occurrence of HCC is to optimize the treatment of NA treated patients with low virus replication and inactive patients with low virus replication to achieve complete virus response and clinical cure. The purpose of this study is to explore the optimal treatment scheme for chronic hepatitis B NA treated patients with hypoviremia and natural low virus replication patients to significantly reduce the risk of HCC.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Chronic hepatitis B seriously endangers the health of our people, especially the occurrence of liver cancer, which brings huge economic burden and life threat to our people. 84% - 92% of hepatocellular carcinoma (HCC) in China is related to chronic HBV infection. How to further reduce the risk of liver cancer is an urgent problem to be solved in clinical research and an important direction. Although NAs treatment can make patients achieve the negative transformation of virus, it can not effectively reduce the level of virus antigen, and it also lacks the ability to improve the immune clearance of virus. As a result, the incidence of liver cancer in patients with long-term NA treatment is still 4.5% - 10.5%, and the incidence of HCC in patients with hypoviremia in Na treatment is higher. In current clinical practice, nearly 1 / 3 of patients treated with NAs can not reach the detection line of highly sensitive reagent. It is an important measure to make the patients with hypoviremia and inactive low virus replication treated by NAs below the detection line of highly sensitive reagent and further reduce the risk of HCC. However, it is still not enough to minimize the risk of HCC to achieve a complete viral response only through NA treatment. The long-term follow-up showed that the incidence of HBsAg disappeared by only 2.0% - 0.0% regardless of the long-term treatment of HBsAg. Therefore, the most important measure to minimize the occurrence of HCC is to optimize the treatment of NA treated patients with low virus replication and inactive patients with low virus replication to achieve complete virus response and clinical cure. The purpose of this study is to explore the optimal treatment scheme for chronic hepatitis B Na treated patients with hypoviremia and natural low virus replication patients to significantly reduce the risk of liver cancer.

Study Type

Observational

Enrollment (Anticipated)

1200

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
    • Beijing
      • Beijing, Beijing, China, 100015
        • Recruiting
        • Department of Hepatology Division 2, Beijing Ditan 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

14 years to 58 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Chronic hepatitis B patients with Hypoviremia after Das therapy

Description

Inclusion Criteria:

  • Aged from 16 to 60;
  • The positive time of HBsAg was 6 months,
  • 48 weeks of treatment with ETV, TDF or TAF, including HBeAg positive and negative patients;
  • High sensitive reagent was used to confirm that the low level of serum HBV DNA was 20 IU / ml-2000 IU / ml.
  • Good compliance and sign informed consent.

Exclusion Criteria:

  1. Patients with decompensated liver cirrhosis or previous decompensated liver cirrhosis;
  2. Those who have used interferon within 6 months;
  3. at the same time, it is associated with other virus infections, such as hepatitis A virus, hepatitis C virus, hepatitis D virus, hepatitis E virus, AIDS virus, etc;
  4. in addition to hepatitis B, there are other serious physical and mental diseases, including uncontrolled primary kidney, heart, lung, vascular, neurological, digestive, severe metabolic diseases (such as uncontrolled hyperthyroidism, serious complications of diabetes and adrenal diseases), immune deficiency diseases, and severe infections; Active or suspected malignant tumor or history of malignant tumor;
  5. 6 months before enrollment or currently receiving corticosteroids, immunosuppressants and chemotherapeutic drugs;
  6. Complicated with alcoholic liver disease, autoimmune liver disease and other liver diseases;
  7. HBV resistant patients;
  8. Other situations that the researcher believes are not suitable for inclusion.

PegIFN α Treatment contraindications:

  1. Prohibited for known pairs α- Patients who are allergic to interferon, E. coli products, polyethylene glycol or any component of this product;
  2. It is forbidden to be used in patients with autoimmune hepatitis;
  3. Pregnant and lactating women;
  4. Central nervous system diseases, mental diseases, uncontrolled epilepsy, non withdrawal of alcohol / drug abuse, decompensated liver cirrhosis, symptomatic heart disease, uncontrolled autoimmune diseases and severe thyroid function diseases;
  5. Absolute neutrophil count before treatment ≤ 1.0 × 109 / L, platelet ≤ 80 × 109/L。

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PEG-IFN optimized treatment group
Patients received optimized treatment of NAs (ETV + TDF or ETV + TAF) combined with PEG-IFN ETV 0.5 mg, TDF 300 mg or TAF 25 mg, oral once a day, PEG-IFN 180 or 135 micrograms, subcutaneous injection once a week, with a personalized course of treatment of 24 weeks.
Drug: PEG-IFN
PEG-IFN 180 or 135 micrograms, subcutaneously injected once a week, with a personalized treatment course of 24 weeks
NAs optimized treatment group
Patients received NAS (ETV + TDF or ETV + TAF) combination therapy and continued NAs maintenance therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of HCC during the project study
Time Frame: 48 weeks
In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The negative conversion rate of HBV DNA after 48 weeks of treatment was optimized (below the detection line of highly sensitive detection reagent)
Time Frame: 48 weeks
In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
48 weeks
The incidence of HBsAg disappearance during the study period;
Time Frame: 48 weeks
In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
48 weeks
HBeAg seroconversion rate in HBeAg positive patients;
Time Frame: 48 weeks
In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
48 weeks
Incidence of chronic hepatitis B during the study period
Time Frame: 48 weeks
In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
48 weeks
To study the incidence of complications such as cirrhotic ascites and upper gastrointestinal bleeding during long-term follow-up.
Time Frame: 48 weeks
In the intervention treatment of the above Na treated patients with hypoviremia, the NAS treatment patients who did not have the disappearance of HBsAg have been maintained for a long time, and long-term treatment and follow-up observation are still carried out after the end of the project. For patients treated with NAS combined with PEG-IFN, if HBsAg disappears, continue the treatment after HBsAg disappears, and stop all drug treatment after 12-24 weeks. For the patients who have not lost HBsAg after PEG-IFN combined with NAS treatment, the researcher shall decide whether to stop all drug treatment or stop PEG-IFN treatment and continue NAS maintenance treatment according to the treatment response.
48 weeks

Collaborators and Investigators

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

Sponsor

Beijing Ditan Hospital

Collaborators

Beijing YouAn Hospital
Beijing 302 Hospital/5th Medical Center of Chinese PLA General Hospital

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 1, 2022

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

April 27, 2022

First Submitted That Met QC Criteria

April 27, 2022

First Posted (Actual)

May 2, 2022

Study Record Updates

Last Update Posted (Actual)

May 12, 2022

Last Update Submitted That Met QC Criteria

May 9, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CFH2022-1-2172

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 Chronic Hepatitis B

Clinical Trials on PEG-IFN

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Belgium

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe