Liver Fibrosis
Conditions
Brief summary
This study was a randomized, double-blind, placebo-controlled, entecavir basic treatment, multicentre clinical study. The main objective of this study was to confirm the efficacy and safety of hydronidone in the treatment of chronic hepatitis B liver fibrosis.
Detailed description
248 patients with chronic viral hepatitis B liver fibrosis were enrolled in this 52-week study, and randomized into hydronidone or placebo group. Each group has 124 patients. Both groups were treated with entecavir antiviral basic therapy.
Interventions
After randomization, the experimental group were orally received hydronidone capsules at a daily dose of 270 mg, 3 capsules each time, t.i.d,30 min before meals for 52 weeks.
After randomization, The control group were orally received placebo capsules at a daily dose of 270 mg, 3 capsules each time, t.i.d, 30 min before meals for 52 weeks.
Sponsors
Beijing Continent Pharmaceutical Co, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age from 18 to 65 years old (including 18 and 65 years old, based on the time of signing the written informed consent); gender is not limited. 2. History of chronic hepatitis B and/or hepatitis B surface antigen (HBsAg) positive≥6 months. 3. Percutaneous liver biopsy confirmed liver fibrosis (Ishak score ≥3). 4. Positive HBV DNA. 5. ALT \< 8 x ULN (standard upper limit). 6. No antiviral therapy with interferon and/or nucleoside analogues within 3 months prior to enrollment. 7. 3 months before inclusion, he/she had not received any of the following proprietary Chinese medicines that may have anti-fibrosis effects: Fuzheng Huayu Capsule (tablet), Anluo Huayu Pill, compound Bijiaruangan tablet, etc. 8. The subject (or his/her sexual partner) had no pregnancy plan during the trial period and within 6 months after the trial, voluntarily used effective physical contraception, and had no sperm or egg donation plan. 9. Before the trial, they have understood the nature, significance, potential benefits, inconvenience and potential dangers of the trial in detail, and have voluntarily participated in the clinical trial, have good communication with the researchers, comply with the requirements of the whole study, and have signed a written informed consent form.
Exclusion criteria
1. Massive upper gastrointestinal hemorrhage within 3 months before enrolment. 2. Total bilirubin (TBiL) \> 3×ULN, or 3×ULN \< ALT \< 8×ULN and TBiL \> 2×ULN. 3. AFP \> 100 μg/L although there was no indication of liver cancer. 4. Platelets (PLT) ≤60×109/L. 5. Prothrombin activity (PTA) \< 50% or INR \> 1.5. 6. Imaging showed obvious space-occupying lesions in the liver, suggesting tumor. 7. Body mass index (BMI) \> 30 kg/m2. 8. Patients with decompensated liver cirrhosis and liver malignant tumor. 9. Patients with chronic hepatitis C or non-viral (alcoholic, non-alcoholic, drug, etc.) chronic hepatitis. 10. Serious diseases of cardiovascular, pulmonary, renal, endocrine, neurological and haematological systems, as well as mental disorders . 11. Women who are pregnant and/or breastfeeding. 12. Have participated in clinical trials of other drugs in the last 3 months. 13. The Investigator considers that there are any conditions that may affect the subjects' informed consent or adherence to the study protocol, or participation in the study may affect the study results or their own safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ishak stage score of liver fibrosis by greater than or equal to 1 point after 52 weeks of treatment relative to baseline. | 52 weeks | Clinically, the liver pathology scoring system, Ishak system, is widely used make a detailed and accurate assessment of the degree of parenchymal fibrosis or cirrhosis of the nontumorous liver. Ishak system uses a scale of 7 stages (scores 0-6) for the degree of fibrosis; the higher the score, the higher degree the severity of the disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in liver tissue inflammation grade by greater than or equal to 1 grade after 52 weeks of treatment relative to baseline. | 52 weeks | Scheuer score system is a liver pathology scoring system used for the diagnosis of liver inflammation and fibrosis pathology clinically; In the present trial, Scheuer system for scoring necroinflammatory activitt in chronic hepatitis will be used(G0-G4),the higher the score, the higher degree the severity of the disease. |
| Change in liver stiffness measurement values via transient elastography LSM (kPa) | Screening period/baseline and weeks 12, 24, 36, and 52 after treatment . | Change in liver stiffness measurement values via transient elastography LSM (kPa) values relative to baseline after 52 weeks of treatment. |
| Negative conversion (below the lower limit of detection) and the extent of decrease in HBV DNA | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | Negative conversion (below the lower limit of detection) and the extent of decrease in HBV DNA after 52 weeks of treatment. |
| Normalization and the degree of improvement of the indicators of liver function ALT after 52 weeks of treatment. | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | ALT is one of the indicators to assess liver function and detect liver damage. When hepatic cells are affected by injury or disease, ALT is released into the blood, resulting in elevated ALT levels in the blood. |
| Safety endpoints:Laboratory examination（AFP test） | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | AFP test: the serum AFP will be detected. |
| Safety endpoints:AE | 52 weeks | Adverse events (AEs) refer to any adverse medical events that occur after the patient takes the study drug and can manifest as signs and symptoms, disease, or abnormal laboratory tests, but are not necessarily consequently related to the study drug. Information on AEs and Concomitant medications occurring in patients will be collected at the time points specified in the study schedule. AEs will be evaluated with reference to the Common Adverse Events Evaluation Criteria (NCI-CTCAE version 5.0). |
| Change in liver inflammation grade by greater than or equal to 1 grade after 52 weeks of treatment relative to baseline but with no progression of fibrosis. | 52 weeks | Scheuer score system is a liver pathology scoring system used for the diagnosis of liver inflammation and fibrosis pathology clinically; In the present trial, Scheuer system for scoring necroinflammatory activitt in chronic hepatitis will be used(G0-G4),the higher the score, the higher degree the severity of the disease. |
| Safety endpoints:Laboratory examination（Metabolic panel-GGT） | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | Metabolic panel: The panel includes gamma-glutamyl transpeptidase (GGT),which is one of the indicators to assess liver function . |
| Safety endpoints:Laboratory examination（Metabolic panel-ALP） | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | Metabolic panel: The panel includes alkaline phosphatase (ALP),which is one of the indicators to assess liver function . |
| Safety endpoints:Laboratory examination（Metabolic panel-TP） | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | Metabolic panel: The panel includes total protein (TP), which is one of the indicators to assess liver function . |
| Safety endpoints:Laboratory examination（Metabolic panel-A） | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | Metabolic panel: The panel includes albumin (A) , which is one of the indicators to assess liver function . |
| Safety endpoints:Laboratory examination（Metabolic panel-TBiL） | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | Metabolic panel: The panel includes total bilirubin (TBiL) , which is one of the indicators to assess liver function . |
| Safety endpoints:Laboratory examination（Metabolic panel-DBiL） | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | Metabolic panel: The panel includes direct bilirubin (DBiL) , which is one of the indicators to assess liver function . |
| Safety endpoints:Laboratory examination（Metabolic panel-AST） | Screening period/baseline and weeks 4, 8, 12, 24, 36, and 52 after treatment. | Metabolic panel: The panel includes aspartate aminotransferase (AST)，which is one of the indicators to assess liver function and detect liver damage. |
Countries
China
Outcome results
None listed