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Study of Entecavir for Reducing the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Patients

Conditions
Chronic Hepatitis B
Registration Number
NCT04646928
Lead Sponsor
CHA University
Brief Summary

To analyze the incidence of liver cancer after entecavir administration among patients with low viral load and cirrhosis due to chronic hepatitis B infection.

Detailed Description

To analyze the incidence of liver cancer after entecavir administration among patients with low viral load (HBV DNA titer\<2,000 IU/mL (104 copies/mL)) and cirrhosis due to chronic hepatitis B infection.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
245
Inclusion Criteria
  • A subject who has consented to participate in this clinical trial

  • A subject aged between ≥20 to ≤75 years old

  • A subject with positive HBsAg for more than 24 weeks (may be confirmed by medical history)

  • HBV DNA ≥26 IU/mL or ≤ 2,000 IU/mL at the time of screening

  • A subject diagnosed with cirrhosis with one of the following:

    1. Subject with confirmed liver cirrhosis in the screening period or liver biopsy performed within 1 year from the time of screening (METAVIR score> 3, ISHAK score> 4)
    2. Two or more confirmed typical findings suggesting liver cirrhosis from imaging such as liver ultrasound and CT performed within 24 weeks of screening or during screening period (nodularity of the liver surface, atrophy of the inner right and left lobes, thickening of the left and tail lobes, hepatic portal system expansion of surrounding space, expansion of hepatic portal system (>1.3 cm) and splenomegaly (>12 cm))
    3. One or more confirmed typical findings suggesting liver cirrhosis from imaging such as liver ultrasound and CT performed within 24 weeks of screening or during screening period (nodularity of the liver surface, atrophy of the inner right and left lobes, thickening of the left and tail lobes, hepatic portal system expansion of surrounding space, expansion of hepatic portal system (>1.3 cm) and splenomegaly (>12 cm)) or findings including the following:
  • Confirmed thrombocytopenia (<150,000/mm3) at the screening period or blood tests conducted within 24 weeks from the time of screening

  • Confirmed identification of esophageal varicose veins or gastric varicose veins by endoscopy or CT performed within one year from the screening period or at screening

  • Liver stiffness measurement (LSM)> 11.5 kilopascal (kPa) (F4) as a result of liver fibrosis scan, performed within 1 year from screening period or at screening

Exclusion Criteria
  • A subject with non compensated cirrhosis and any of the following:

    1. Serum bilirubin> 3 mg/dL
    2. Prothrombin time> 6 seconds prolonged or International Normalized Ratio (INR) >1.6
    3. Serum albumin <2.8 g/dL
    4. History of ascites, varicose bleeding, hepatorenal syndrome, hepatic encephalopathy (hepatic coma) requiring treatment within 5 years from screening
    5. Child-Pugh score ≥ 8
  • A subject who have received interferon or other oral nucleic acid analogues (nucleos(t)ide analogues) (However, if the treatment duration was less than 30 days in the past and the treatment was treated 24 weeks before the screening, participation is possible)

  • A subject diagnosed with liver cancer in the past or present

  • Renal function decline (creatinine clearance <50 mL/min, estimated by the Cockcroft-Gault formula)

  • A subject with serious concomitant diseases such as congestive heart failure, chronic kidney disease, blood disease, or malignant tumors in the past or present

  • A subject infected with hepatitis C virus (HCV) or human immunodeficiency virus (HIV)

  • A subject who consume excessive alcohol (men: 30g/day or more, women: 20g/day or more)

  • A subject with liver diseases such as autoimmune hepatitis, hemochromatosis, or Wilson's disease

  • Pregnant or breastfeeding women

  • Previous organ transplant recipients

  • A subject unable to complete the clinical trial or to have any medical condition that may interfere with the evaluation of the efficacy of this clinical trial

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
5-year Cumulative hepatocellular carcinoma incidence5 years

Compare the difference in the 5-year cumulative incidence of hepatocellular carcinoma in patients with chronic hepatitis B and cirrhosis with entecavir and control

Secondary Outcome Measures
NameTimeMethod
Overall Survival5 years

Compare the difference in the 5-year incidence overall survival in patients with chronic hepatitis B and cirrhosis with entecavir and control

Incidence of ascites, esophageal, gastric variceal bleeding, hepatic encephalopathy (hepatic coma)5 years

Compare the difference in the 5-year incidence of ascites/esophageal/gastric variceal bleeding/hepatic encephalopathy (hepatic coma) in patients with chronic hepatitis B and cirrhosis with entecavir and control

Incidence of virologic response, virologic breakthrough5 years

Compare the difference in the 5-year incidence incidence of virologic response and virologic breakthrough in patients with chronic hepatitis B and cirrhosis with entecavir and control

Incidence of cirrhosis regression5 years

Compare the difference in the 5-year incidence of cirrhosis regression in patients with chronic hepatitis B and cirrhosis with entecavir and control

Trial Locations

Locations (11)

Soon Chun Hyang University Hospital Bucheon

🇰🇷

Bucheon, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Gyeonggi-do, Korea, Republic of

The Catholic University of Korea, St. Vincent's Hospital

🇰🇷

Suwon, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Soon Chun Hyang University Hospital Cheonan

🇰🇷

Cheonan, Korea, Republic of

CHA Bundang Medical Center

🇰🇷

Gyeonggi-do, Korea, Republic of

Bundang Jesaeng Hospital

🇰🇷

Gyeonggi-do, Korea, Republic of

Catholic University of Korea, Uijeongbu ST. Mary's Hospital

🇰🇷

Gyeonggi-do, Korea, Republic of

Ajou University Hospital

🇰🇷

Suwon, Korea, Republic of

Gachon University, Donginchoen Gil Hospital

🇰🇷

Sŏngnam, Korea, Republic of

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