Magnesium Isoglycyrrhizinate Followed by Diammonium Glycyrrhizinate and Combined With Entecavir in Chronic Hepatitis B

Study Overview
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Brief Summary
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This study evaluates the addition of glycyrrhizin to entecavir in the treatment of patients with chronic hepatitis B in China. Half of participants will receive magnesium isoglycyrrhizinate followed by oral diammonium glycyrrhizinate and entecavir in combination, while the other half will receive a placebo and entecavir.

Detailed Description
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Chronic hepatitis B(HBV) has a high prevalence (>8%) in China. Entecavir, aguanosine analog, is a potent and selective inhibitor of HBV DNA polymerase. Glycyrrhizin has been used for more than 30 years in the treatment of liver diseases in Asian countries, who can relieve necro-inflammatory and liver fibrosis or cirrhosis Recent study has shown that inflammation plays the important role in chronic HBV and fibrosis or cirrhosis disease progression, but antiviral therapy only may not reduce inflammation ideally. The addition of glycyrrhizin to entecavir in the treatment may slow disease progression in patients with chronic HBV and advanced fibrosis or cirrhosis.

Official Title
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The Efficacy and Safety Study of Magnesium Isoglycyrrhizinate Injection Followed by Diammonium Glycyrrhizinate Enteric-coated Capsules and Combined With Entecavir on the Treatment of Chronic Hepatitis B

Conditions
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Chronic Hepatitis b, Liver Inflammation

Intervention / Treatment
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* Drug: Entecavir
* Drug: Magnesium Isoglycyrrhizinate
* Drug: Diammonium Glycyrrhizinate
* Drug: Magnesium Isoglycyrrhizinate Placebo
* Drug: Diammonium Glycyrrhizinate Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hepatitis B surface antigen [HBsAg]-positive, Either hepatitis B e antigen (HBeAg)-positive or HBeAgnegative/hepatitis B e antibody (HBeAb)-positive disease were eligible, Serum alanine aminotransferase (ALT) levels 3-10×the upper limit of normal (ULN),serum total bilirubin(TBIL)levels<2×ULN Exclusion Criteria: Co-infection with hepatitis C virus, hepatitis D virus, or human immunodeficiency virus; Other forms of liver disease; More than 24 weeks of therapy with a nucleoside or nucleotide analog with activity against HBV, and therapy with any anti-HBV drug within 24 weeks prior to randomization; More than 12 weeks of therapy with liver protectants, and therapy with glycyrrhizin; Has decompensated liver function or has a hint of hepatocellular carcinoma (HCC); During the study patients were not allowed to use other medicines.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Entecavir treatment with placebo, Magnesium Isoglycyrrhizinate placebo followed by Diammonium Glycyrrhizinate placebo | Drug: Entecavir<br>* Glycyrrhizin for the treatment of patients with chronic hepatitis B combined with entecavir-based<br>* Other names: Entecavir Pill;Drug: Magnesium Isoglycyrrhizinate Placebo<br>* Magnesium Isoglycyrrhizinate Injection Placebo<br>* Other names: Magnesium Isoglycyrrhizinate Injection Placebo;Drug: Diammonium Glycyrrhizinate Placebo<br>* Diammonium Glycyrrhizinate Enteric-coated Capsules Placebo<br>* Other names: Diammonium Glycyrrhizinate Enteric-coated Capsules Placebo;|
| Experimental: Experimental group<br>Entecavir combined with glycyrrhizin, Magnesium Isoglycyrrhizinate Injection followed by Diammonium Glycyrrhizinate | Drug: Entecavir<br>* Glycyrrhizin for the treatment of patients with chronic hepatitis B combined with entecavir-based<br>* Other names: Entecavir Pill;Drug: Magnesium Isoglycyrrhizinate<br>* Magnesium Isoglycyrrhizinate Injection treat for two weeks with entecavir-based<br>* Other names: Magnesium Isoglycyrrhizinate Injection;Drug: Diammonium Glycyrrhizinate<br>* Diammonium Glycyrrhizinate for oral after Magnesium Isoglycyrrhizinate Injection treatment with entecavir-based<br>* Other names: Diammonium Glycyrrhizinate Enteric-coated Capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of ALT(Alanine aminotransferase) | The ALT levels of plasma are measured at baseline and at 24 weeks. The normal value was 0-40 U/L. | baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Liver inflammatory | Liver inflammatory of the liver biopsies is performed at baseline and 24 weeks evaluated by Knodell HAI score. | baseline and 24 weeks | 
| Change of Liver Fibrosis | Liver Fibrosis is performed at baseline and 96 weeks evaluated by Fibroscan examination. | baseline and 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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necro-inflammatory, glycyrrhizin, entecavir, hepatic biological parameters, liver fibrosis