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

Phase 4

• Conditions: Chronic Hepatitis b; Liver Inflammation
• Interventions: Drug: Entecavir; Drug: Magnesium Isoglycyrrhizinate Placebo; Drug: Magnesium Isoglycyrrhizinate; Drug: Diammonium Glycyrrhizinate Placebo; Drug: Diammonium Glycyrrhizinate

• Registration Number: NCT03349008
• Lead Sponsor: Cttq

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-05-04
• Status Verified: 2017-11
• Study First Submitted QC: 2017-11-16
• Last Update Submitted: 2017-11-16
• Study First Posted: 2017-11-21
• Last Update Posted: 2017-11-21
• Study Start: 2017-11-25
• Primary Completion: 2019-12-31
• Study Completion: 2020-05-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 480

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Entecavir	Entecavir treatment with placebo, Magnesium Isoglycyrrhizinate placebo followed by Diammonium Glycyrrhizinate placebo
Control group	Magnesium Isoglycyrrhizinate Placebo	Entecavir treatment with placebo, Magnesium Isoglycyrrhizinate placebo followed by Diammonium Glycyrrhizinate placebo
Control group	Diammonium Glycyrrhizinate Placebo	Entecavir treatment with placebo, Magnesium Isoglycyrrhizinate placebo followed by Diammonium Glycyrrhizinate placebo
Experimental group	Entecavir	Entecavir combined with glycyrrhizin, Magnesium Isoglycyrrhizinate Injection followed by Diammonium Glycyrrhizinate
Experimental group	Magnesium Isoglycyrrhizinate	Entecavir combined with glycyrrhizin, Magnesium Isoglycyrrhizinate Injection followed by Diammonium Glycyrrhizinate
Experimental group	Diammonium Glycyrrhizinate	Entecavir combined with glycyrrhizin, Magnesium Isoglycyrrhizinate Injection followed by Diammonium Glycyrrhizinate

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change of Liver inflammatory	baseline and 24 weeks	Liver inflammatory of the liver biopsies is performed at baseline and 24 weeks evaluated by Knodell HAI score.
Change of Liver Fibrosis	baseline and 96 weeks	Liver Fibrosis is performed at baseline and 96 weeks evaluated by Fibroscan examination.