Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment

Study Overview
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Brief Summary
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This study aims to investigate the efficacy and safety of avatrombopag for treating thrombocytopenia in hepatitis b virus related acute-on-chronic liver failure patients receiving artificial liver support system treatment.

Detailed Description
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Artificial liver support system (ALSS) is an optimal therapy in patients with hepatitis b virus (HBV) related acute-on-chronic liver failure (ACLF). But a lot of patients encount thrombocytopenia (TCP) due to the mechanical damage of thrombocyte and use of heparin during the treatment. Avatrombopag is an oral thrombopoietin receptor agonist that has been recently approved for treating TCP in chronic liver disease patients needing invasive procedures. Therefore, this study aims to investigate the efficacy and safety of avatrombopag for treating TCP in HBV related ACLF patients receiving ALSS treatment. Sixty patients with HBV related ACLF receiving ALSS will be enrolled in this study. The participants are divided into trial group (avatrombopag, double plasma molecular adsorption system (DPMAS) , low volume plasma exchange (LPE), and comprehensive internal medical treatment) and control group (DPMAS, LPE, comprehensive internal medical treatment). Symptoms, signs, laboratory tests results, adverse events, mortality rates are recorded from treatment baseline to 3 weeks.

Official Title
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Efficacy and Safety of Avatrombopag for Treating Thrombocytopenia in Hepatitis b Virus Related Acute-on-chronic Liver Failure Patients Receiving Artificial Liver Support System Treatment

Conditions
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Thrombocytopenia, Hepatitis B, Chronic, Acute-On-Chronic Liver Failure

Intervention / Treatment
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* Drug: Avatrombopag
* Other: Artificial Liver Support System
* Other: Comprehensive internal medical treatment.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 65 years old; Clinical diagnosis of chronic hepatitis b virus infection (positive hepatitis b surface antigen or positive hepatitis b virus DNA > 0.5 year); Clinical diagnosis of liver failure (serum total bilirubin level > 10 times upper limit of normal; prothrombin time activity < 40% and ≥20%, or prothrombin time international ratio ≤ 2.6 and > 1.5); Platelets < 80*10 E9/L and > 50*10 E9/L. Signed informed consent form. Exclusion Criteria: Other active liver diseases; Hepatocellular carcinoma or other malignancy; Pregnancy or lactation; Human immunodeficiency virus infection or congenital immune deficiency diseases; Severe diabetes, autoimmune diseases; unstable infarction due to cardio-cerebrovascular events; other important organ dysfunctions or transplantation; Severe complications including severe infection, gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome; Patients with ALSS treatment in one week; Thrombotic disease; Patients can not follow-up; Investigator considering inappropriate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trial Group<br>30 patients receive treatment of avatrombopag, DPMAS, LPE, and comprehensive internal medical treatment. | Drug: Avatrombopag<br>* Patients will receive treatment of oral avatrombopag 20mg per day for the first 5 days<br>Other: Artificial Liver Support System<br>* Patients will receive treatment of double plasma molecular adsorption system (DPMAS) and low volume plasma exchange (LPE) for three times. The volume of plasma adsorption in DPMAS is 5000 6000 millilitre. The volume of fresh frozen plasma used in LPE is 1000 millilitre.<br>Other: Comprehensive internal medical treatment.<br>* Patients will receive comprehensive internal medical treatment.<br>|
| Active Comparator: Control Group<br>30 patients receive treatment of DPMAS, LPE, and comprehensive internal medical treatment. | Other: Artificial Liver Support System<br>* Patients will receive treatment of double plasma molecular adsorption system (DPMAS) and low volume plasma exchange (LPE) for three times. The volume of plasma adsorption in DPMAS is 5000 6000 millilitre. The volume of fresh frozen plasma used in LPE is 1000 millilitre.<br>Other: Comprehensive internal medical treatment.<br>* Patients will receive comprehensive internal medical treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of platelet ≥50*10E9/L | Rate of patients with platelet ≥50*10E9/L during ALSS treatment | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of bleeding | Incident rate of patients with bleeding during treatment | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thrombocytopenia, hepatitis B virus, acute-on-chronic liver failure, double plasma molecular adsorption system, plasma exchange, artificial liver support system