The Efficacy and Safety of Thymosin-α1 in Patients With HBV-related ACLF

Study Overview
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Brief Summary
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A randomized controlled trial to evaluate efficacy and safety of Thymosin-α1 administration in patients with HBV-related Acute-on-chronic liver failure.

Detailed Description
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Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is a severe disease with high mortality. In this study, the investigators intend to assess the efficacy and safety of Thymosin-α1 in patients with HBV-related Acute-on-chronic liver failure.

Official Title
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A Randomized Controlled Trial to Evaluate Efficacy and Safety of Thymosin-α1 Administration in Patients With HBV-related Acute-on-chronic Liver Failure

Conditions
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Liver Failure

Intervention / Treatment
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* Drug: Thymosin-α1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Chronic hepatitis B.(Hepatitis B surface antigen positive for more than 6 months or having evidence of chronic hepatitis B virus infection). 2.Defined by an acute deterioration in transaminase greater than or equal to 5 times upper normal limit over14 days. 3.Development of jaundice (serum bilirubin greater than or equal to 10mg/dl). 4.Development of coagulopathy(PTA≤40% or INR≥1.5 ). More than one of the 5-8 criteria： 5.Development of hepatic encephalopathy. 6.Development of hepatorenal syndrome. 7.Hepatic narrowing progressively. 8.Development of massive ascites or peritonitis. 9. Willing to provide informed consent and comply with the test requirements Exclusion Criteria: 1.Patients who have hepatocellular carcinoma confirmed by ultrasound/CT/MR. 2.Patients who have autoimmune disease (such as inflammatory bowel disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, etc ) or with abnormal elevation level of autoimmune antibody. 3.Model for end-stage liver disease (MELD) score <17 or >35. 4.Patients with significant co-morbid illnesses such as cardiovascular or respiratory or intrinsic renal diseases which by themselves may have a bearing on the outcome. 5.Patients with diseases that researchers consider inappropriate to participate in the study. 6.Patients who have disseminated intravascular coagulation. 7.Drug allergy. 8.Patients with any other contraindications to thymosin alpha1. 9.Patients who participated in other clinical trials at the same time.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thymosin-α1 group<br>Patients receive treatment based on standard Therapy with additional Thymosin-α1 | Drug: Thymosin-α1<br>* 1.6 mg s.c injection once per day for 7 days, then 1.6 mg s.c injection twice a week for 11 weeks.<br>* Other names: Zadaxin;|
| No Intervention: control group<br>Patients receive treatment based on standard Therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The liver transplantation-free survival rate of 90 days | Survival condition of the patients were observed for 90 days | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The liver transplantation-free survival rate of 180 days | Survival condition of the patients were observed for 180 days | 180 days | 
| Number of participants with ferver, bleeeding of injection site, amyotrophy and arthralgia | Fever, bleeeding of injection site, amyotrophy and arthralgia were observed during the treatment in both group. | 24 weeks | 
| Complications after 48 hours admission | Occurence of encephalopathy, infection, bleeding,hepatorenal syndrome after 48 hours admission. | 24 weeks | 
| Hepatitis B virus DNA load change | Hepatitis B virus DNA were measured on week 0, 4,8,12 and 24 after the start of the infusion in both groups | 24 weeks | 
| Causes of death/liver transplantation | Causes of death/liver transplantation (e.g. liver failure, multiple organs failure, severe infection) were recorded in both groups. | 24 weeks | 
| Inflammatory indexes change | Inflammatory indexes were measured on week0,1,2, 4,8,12 and 24 after the start of the infusion in both groups | 24 weeks | 
| Alanine aminotransferase change | Levels of alanine aminotransferase were measured on week0,1,2, 4,8, 12 and 24 after the start of the infusion in both groups | 24 weeks | 
| Glutamic oxaloacetic transaminase change | Levels of glutamic oxaloacetic transaminase were measured on week0,1,2, 4,8, 12 and 24 after the start of the infusion in both groups | 24 weeks | 
| Total bilirubin change | Levels of total bilirubin were measured on week0,1,2, 4,8,12 and 24 after the start of the infusion in both groups | 24 weeks | 
| Plasma thrombin time change | Levels of plasma thrombin time were measured on week0,1,2, 4,8,12 and 24 after the start of the infusion in both groups | 24 weeks | 
| Albumin time change | Levels of albumin were measured on week0,1,2, 4,8, 12 and 24 after the start of the infusion in both groups | 24 weeks |