Efficacy and Safety of ALSS Treatment for ICIs-LF in Patients With HCC

Efficacy and Safety of Artificial Liver Support System Treatment for Immune Checkpoint Inhibitors Related Liver Failure in Patients With Hepatocellular Carcinoma

This study aims to investigate the efficacy and safety of artificial liver support system treatment for immune checkpoint inhibitors related liver failure in patients with hepatocellular carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Liver Failure; Hepatocellular Carcinoma; Immune-Mediated Hepatitis
• Intervention / Treatment: Other: DPMAS+LPE; Other: Comprehensive internal medical treatment; Other: PE

Detailed Description

Immune checkpoint inhibitors (ICIs) are commonly used for advanced stage of hepatocellular carcinoma (HCC) in recent years. The incident rate of Grade 4 immune checkpoint inhibitors-induced immune mediated hepatitis reaches 14.5%. Since these patients usually develop into liver failure, it is urgent to find out a more suitable therapy. Artificial liver support system (ALSS) treatment has been proved to effectively control both immune mediated hepatitis and liver failure, it may be a new therapy for immune checkpoint inhibitors-induced liver failure (ICIs-LF) in patients with HCC. Therefore, this study aims to investigate the efficacy and safety of ALSS treatment, including the classic mode of plasma exchange (PE) and new combination mode of double plasma molecular adsorption system (DPMAS) with sequential low-dose plasma exchange (LPE), for ICIs-LF in patients with HCC. Sixty patients with HCC and ICIs-LF will be enrolled in this study. The participants are randomly divided into trial group (DPMAS+LPE, and comprehensive internal medical treatment) and control group (PE and comprehensive internal medical treatment). Symptoms, signs, laboratory tests results, adverse events, mortality rates are recorded from treatment baseline to 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wenxiong Xu, Doctor; Phone Number: +8613760783281; Email: xuwenx@mail.sysu.edu.cn
• Study Contact Backup: Name: Liang Peng, Doctor; Phone Number: +8613533978874; Email: pliang@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • Third Affiliated Hospital of Sun Yat-sen University
      • Contact: Wenxiong Xu, Doctor; Phone Number: +8613760783281; Email: xuwenx@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age from 18 to 65 years old;
2. Clinical diagnosis of chronic hepatitis b virus infection (positive hepatitis b surface antigen or positive hepatitis b virus DNA > 0.5 year);
3. Clinical diagnosis of hepatocellular carcinoma and receive immune checkpoint inhibitors treatment. The last treatment of immune checkpoint inhibitors is less than three months from inclusion;
4. The level of hepatitis b virus DNA < 2000 IU/mL；
5. Serum aspartate aminotransferase/alanine aminotransferase > 20 times upper limit of normal；serum total bilirubin>10 times upper limit of normal；
6. Prothrombin time international ratio > 1.5;
7. Platelets > 50*10 E9/L;
8. Without intrahepatic bile duct dilation due to tumor progression.

Exclusion Criteria:

1. Other active liver diseases;
2. Other malignancy;
3. Pregnancy or lactation;
4. Human immunodeficiency virus infection or congenital immune deficiency diseases;
5. Severe diabetes, autoimmune diseases; unstable infarction due to cardio-cerebrovascular events; other important organ dysfunctions or transplantation;
6. Active bleeding, disseminated intravascular coagulation, thrombosis, or thrombotic disease;
7. Patients received artificial liver support system treatment in one week before inclusion;
8. Patients can not follow-up;
9. Investigator considering inappropriate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DPMAS+LPE group; 30 patients receive treatment of DPMAS, LPE, and comprehensive internal medical treatment.	Other: DPMAS+LPE; Patients will receive treatment of double plasma molecular adsorption system (DPMAS) and low volume plasma exchange (LPE) for three times in two weeks. The volume of plasma adsorption in DPMAS is 5000~6000 millilitre. The volume of fresh frozen plasma used in LPE is 1000 millilitre.; Other: Comprehensive internal medical treatment; Patients will receive comprehensive internal medical treatment.
Active Comparator: PE group; 30 patients receive treatment of PE and comprehensive internal medical treatment.	Other: Comprehensive internal medical treatment; Patients will receive comprehensive internal medical treatment.; Other: PE; Patients will receive treatment of plasma exchange (PE) for three times in two weeks. The volume of fresh frozen plasma used in PE is 2000 millilitre.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate	Mortality rate at 12-week follow-up.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Model for end-stage liver disease (MELD) score variation	Variation of MELD score at 12 weeks after treatment. MELD score = 9.57 × loge(creatinine mg/dl) + 3.78 × loge(TBIL mg/dl) + 11.20 × loge(PT-INR) + 6.43.	12 weeks

Collaborators and Investigators

• Sponsor: Third Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Wenxiong Xu, Doctor, Third Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 30, 2022
• First Submitted That Met QC Criteria: July 30, 2022
• First Posted (Actual): August 2, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: XWX4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol, results and conclusions of this clinical trial will be published at academic conferences or in journals.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: Proposals should be directed to xuwenx@mail.sysu.edu.cn. To gain access, data requestors will need to sign a data access agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No