A Prospective Study to Evaluate Peginterferon in Reducing the Incidence of HCC in CHB Patients
A Prospective, Randomized, Open-label, Multicenter Study to Evaluate the Peginterferon, Comparing to Nucleos(t)Ide Analogues, in Reducing the Incidence of HCC in Chronic Hepatitis B Patients With Intermediate to High Liver Cancer Risks
1 other identifier
interventional
267
1 country
9
Brief Summary
China's new cases and deaths of hepatocellular carcinoma (HCC) rank first in the world. hepatocellular carcinoma is the third most morbid, second-most mortal malignancy in China. Up to 80% of hepatocellular carcinoma patients caused by HBV infection. Antiviral therapy can significantly reduce the incidence and mortality of hepatocellular carcinoma in patients with chronic hepatitis B (CHB), hinder the progression of liver disease, and effectively control the disease. However, studies in recent years have found that long-term therapy with Nucleos(t)ide analogue (NAs) cannot completely eliminate the risk of liver cancer in patients with chronic hepatitis B. In addition, a number of retrospective studies at home and abroad have shown that compared with long-term oral NAs, peginterferon can significantly reduce the risk of hepatocellular carcinoma in patients with chronic hepatitis B. However, there is limit prospective studies. This multicenter, randomized, open-label, controlled trial study is aim to evaluate the pegylated interferon alfa-2b injection in comparing to NAs in reducing the incidence of hepatocellular carcinoma, to provide evidences for new management and treatment strategy options for improving clinical outcomes for the chronic hepatitis B patients. About 267 chronic hepatitis patients with intermediate to high risk of liver cancer who are now receiving nucleoside therapy will be enrolled. Subjects will be randomized into the peginterferon combined NAs group and the NAs monotherapy group at a ratio of 2:1. Level of HBsAg, proportion of patients with HBsAg clearance and seroconversion, incidence of liver cirrhosis and hepatocellular carcinoma will be assessed.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Jul 2019
Longer than P75 for not_applicable
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 3, 2019
CompletedFirst Submitted
Initial submission to the registry
March 15, 2020
CompletedFirst Posted
Study publicly available on registry
January 4, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2026
CompletedMay 25, 2023
May 1, 2023
4.1 years
March 15, 2020
May 23, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change of HBsAg level compared to baseline
week 48 of treatment
Secondary Outcomes (4)
Proportion of patients with HBsAg clearance
At week 48 of treatment and 5 years of follow up
Proportion of patients with HBsAg seroconversion
At week 48 of treatment and 5 years of follow up
Proportion of patients with change of liver stiffness measurement (LSM)
At week 48 of treatment and 5 years of follow up
Incidence of liver cirrhosis and hepatocellular carcinoma
At week 48 of treatment and 5 years of follow up
Study Arms (2)
Combined treatment group
EXPERIMENTALPeginterferon alfa-2b Injection combined Nucleos (t) ide Analogue therapy
Monotherapy group
ACTIVE COMPARATORNucleos (t) ide Analogue monotherapy
Interventions
1.Peginterferon alfa-2b injection: 180μg, subcutaneously inject, once a week, from week 1 to Week 48. 2, NAs: Dose please follow the approved dosage, once daily, from the first day until when discontinuation is indicated. NAs Discontinuation Criteria: A total course of treatment is recommended for at least 4 years, and discontinuation may be considered if HBV DNA is below the lower limit of detection, Alanine aminotransferase renormalization, and HBeAg serological conversion, and remain unchanged (test every 6 months) during a consolidation therapy for at least 3 years. However, a prolonged course of treatment may reduce relapse.
NAs: Dose please follow the approved dosage, once daily, from the first day until when discontinuation is indicated. NAs Discontinuation Criteria: A total course of treatment is recommended for at least 4 years, and discontinuation may be considered if HBV DNA is below the lower limit of detection, Alanine aminotransferase renormalization, and HBeAg serological conversion, and remain unchanged (test every 6 months) during a consolidation therapy for at least 3 years. However, a prolonged course of treatment may reduce relapse.
Eligibility Criteria
You may qualify if:
- Aged 18 to 60 years and no gender limit (including 18 and 60 years).
- HBsAg positive for more than 6 months.
- Patients with intermediate to high liver cancer risks. Refers to if at least one of the following items is met.
- Male patient aged above 40 years.
- Patients with a history of cirrhosis and/or family history of liver cancer.
- Patients with metabolic diseases, such as diabetes, fatty liver, etc.
- Any liver cancer assessment model of chronic hepatitis B patients suggested that liver cancer was at intermediate to high risk.
- Have received Nucleos(t)ide analogue treatment for more than 24 weeks, and currently receiving Nucleos(t)ide analogue, while HBV DNA is undetectable (HBV DNA below 300 IU/mL or 1000 copies/mL).
- Urine and/or serum pregnancy test within 24 hours prior to the first dose must be negative for female patients of childbearing potential.
- Understand and voluntarily sign informed consent form.
You may not qualify if:
- Patients co-infected with active hepatitis A, hepatitis C, hepatitis D, hepatitis E or HIV.
- Patients who have previously received interferon therapy.
- Alpha-fetoprotein greater than 100 ng/mL at screening, or liver imaging suggestive of liver tumor.
- Decompensated liver disease (Child-Pugh score ≥ 5).
- Pregnant or lactating women or patients planning to become pregnant or cannot to take contraception during the study.
- Neutrophil count \< 1.5 x 109/L, platelet count \< 90 x 109 cells/L, or Creatinine 1.5 times higher than the upper limit of normal.
- Patients with severe psychiatric history, particularly depression.
- History of immune-mediated disease or levels of autoimmune antibodies markedly elevated.
- Patients with severe diseases in major organ, such as heart, lung, kidney, brain, blood, etc., and patients with malignancies.
- Patients with poorly controlled diabetes, hypertension, and thyroid disease.
- Patients with history of severe retinopathy or other evidence of retinopathy.
- Patient who ever received organ transplantation, or planning to receive organ transplantation.
- Patients who are allergic to interferon or any of its ingredients.
- Other circumstances that the investigator deems inappropriate to participate in this study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Qing XIelead
Study Sites (9)
The Public Health Clinical Center Of Chengdu
Chengdu, China
The First Affiliated Hospital of USTC Anhui Provincial Hospital
Hefei, China
The Affiliated Hospital of Qingdao University
Qingdao, China
Ruijin Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, China
Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, China
Tongren Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, China
The Fifth People's Hospital Of Suzhou
Suzhou, China
Xiamen Hospital of Traditional Chinese Medicin
Xiamen, China
The Tirth Affiliated Hospital Of Xinxiang Medical University
Xinxiang, China
Related Publications (1)
Jiang S, Guo S, Huang Y, Xu J, Li Y, Zeng Y, Guo Y, Ouyang L, Zhu C, Zhao W, Zhang Q, Guo Q, Xin H, Xie Q. Interim analysis of the PARADISE study: Benefits of add-on peginterferon-alpha in NA-treated patients with CHB. Antiviral Res. 2024 Jun;226:105892. doi: 10.1016/j.antiviral.2024.105892. Epub 2024 Apr 23.
PMID: 38663455DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Qing Xie
Ruijin Hospital, Shanghai
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Director of Department of Infectious Disease, Rui Jin Hospital
Study Record Dates
First Submitted
March 15, 2020
First Posted
January 4, 2023
Study Start
July 3, 2019
Primary Completion
August 1, 2023
Study Completion
April 1, 2026
Last Updated
May 25, 2023
Record last verified: 2023-05