Efficacy and Safety of Cytokine Adsorption and Plasma Exchange in Patients With ACLF and Sepsis

Efficacy and Safety of Double Plasma Cytokine Adsorption System With Sequential Low-Dose Plasma Exchange in Treating Acute-on-Chronic Liver Failure and Sepsis: A Multi-center Randomized Controlled Study

This study aims to evaluate the efficacy and safety of the double plasma cytokine adsorption system with sequential low-dose plasma exchange (DPCAS+LPE) in patients with acute-on-chronic liver failure (ACLF) complicated by sepsis. The focus is on assessing the impact of the cytokine adsorption column(CA280,Jafron Biomedical Co., Ltd., Zhuhai, China) on survival rates, inflammation markers, and organ function to determine its potential value in clinical practice.

The primary research questions are: (1) Does DPCAS+LPE artificial liver therapy improve the 4-week mortality rate in ACLF patients with sepsis? (2) Does it improve the 12-week mortality rate in these patients? Additionally, the study examines the effects of this therapy on APACHE II scores, SOFA scores, vasoactive-inotropic score, MELD scores, and COSSH-ACLF II scores, as well as the cytokine adsorption efficiency of the CA280.

Patients were randomly assigned to either the DPCAS+LPE group or the plasma exchange(PE) group. All patients received artificial liver therapy every other day, for a total of two sessions. Follow-up assessments were conducted before and after each therapy session, as well as at 1, 2, 3, 4, and 12 weeks.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Acute-On-Chronic Liver Failure
• Intervention / Treatment: Other: plasma exchange; Device: double plasma cytokine adsorption system with sequential low-dose plasma exchange

• Study Type: Interventional
• Enrollment (Estimated): 192
• 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: Liang Peng, Doctor; Phone Number: +8613533978874; Email: pzp33@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18 and 70 years with a background of chronic liver disease, regardless of the presence of cirrhosis.
2. Total bilirubin (TBIL) > 12 mg/dL.
3. International normalized ratio (INR) ≥ 1.5.
4. Meeting the diagnostic criteria for sepsis: confirmed or suspected infection, with a sequential organ failure assessment (SOFA) score increase of ≥ 2 points. (5) High inflammatory status: IL-6 > 80 pg/ml.

(6) Diagnosis of sepsis within the past 72 hours.

Exclusion Criteria:

1. Inherited metabolic liver disease (including Wilson's disease, hereditary hemochromatosis, and alpha-1 antitrypsin deficiency).
2. Patients with hepatocellular carcinoma or other malignancies.
3. Pregnant or breastfeeding women.
4. Patients with human immunodeficiency virus (HIV) infection or other immunodeficiency diseases (including active hematological malignancies, congenital immunodeficiency syndromes, or those currently receiving high-dose systemic immunosuppressive therapy).
5. Unstable phase of cerebrovascular events.
6. History of organ transplantation.
7. Patients with irreversible or terminal extrahepatic organ failure that precludes safe extracorporeal circulation or confounds the intervention: ①Terminal chronic obstructive pulmonary disease, terminal cor pulmonale, brain death, or persistent vegetative state, or Grade IV hepatic encephalopathy. ②Requirement for renal replacement therapy (RRT) at the time of screening/enrollment. ③Despite adequate fluid resuscitation, vasopressors, and steroid treatment, unable to maintain mean arterial pressure above 65 mmHg.
8. Platelet count < 50×10E9/L, severe coagulation disorders (INR>3.5), or active bleeding.
9. Known allergies to extracorporeal circulation, hemoperfusion, or other severe allergic history.
10. Refusal by the patient or their legally authorized representative (LAR) to participate in the study, or sign the informed consent form.
11. Inability to return for regular follow-up visits as planned in the study.
12. Other conditions that, in the judgment of the researchers, make the patient unsuitable for enrollment.

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: Double plasma cytokine adsorption system with sequential low-dose plasma exchange; 96 patients in this group will receive standard medical treatment, double plasma cytokine adsorption system with sequential low-dose plasma exchange (DPCAS+LPE) for two sessions, and plasma exchange(PE) for the third session.	Device: double plasma cytokine adsorption system with sequential low-dose plasma exchange; Both groups received comprehensive medical treatment, including antiviral therapy, anti-infection treatment, supportive care, symptomatic treatment, and prevention of complications. All patients will initiate ALSS within 48 hours of enrollment, with treatment administered every other day, for a total of three sessions. The experimental group： The first two sessions consisted of a double plasma cytokine adsorption system with sequential low-dose plasma exchange (DPCAS+LPE). This involved using a cytokine adsorption column (CA280,Jafron Biomedical Co., Ltd., Zhuhai, China) and a bilirubin adsorption device (BS330,Jafron Biomedical Co., Ltd., Zhuhai, China) on the same treatment circuit. DPCAS treatment was performed first, with an adsorption volume of 4500ml to 5000ml over 2 to 3 hours, followed by plasma exchange (PE), with 1000ml of plasma and 500ml of 4% albumin being infused. The third treatment was plasma exchange, with the same dosing as in the control group.
Active Comparator: Plasma exchange; 96 patients in this group will receive standard medical treatment and plasma exchange(PE) for three sessions.	Other: plasma exchange; Based on comprehensive medical treatment, the control group received plasma exchange(PE) treatment, where whole blood was processed through a plasma separator (MICROPLAS MPS 07, BELLCO S.R.L., Italy), with a portion of the plasma discarded and replaced with 1000ml of plasma and 500ml of 4% albumin.Three sessions of plasma exchange (PE) performed every other day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate	4-week mortality rate	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate	12-week Mortality rate	12 weeks
Changes in Acute Physiology and Chronic Health Evaluation II score from baseline	The theoretical maximum value of Acute Physiology and Chronic Health Evaluation II score（APACHE II score） was 71 points. The higher the score, the higher the risk of death. Patients with more than 15 points were classified as severe, and patients with less than 15 points were classified as non-severe.	1, 2, 3, and 4 weeks
Changes in sequential organ failure assessment score from baseline	The theoretical value range of sequential organ failure assessment（SOFA） score is 6-24. The higher the score, the worse the prognosis.	1, 2, 3, and 4 weeks
Changes in vasoactive-inotropic score from baseline	Vasoactive-Inotropic Score ( VIS ) evaluates cardiac function and the intensity of vasoactive drug therapy in critically ill patients by quantifying the dose of vasoactive and inotropic drugs received by patients. VIS has no special value range. The higher the score, the higher the patient 's dependence on vasoactive drugs.	1, 2, 3, and 4 weeks
Changes in Model for End-Stage Liver Disease score from baseline	MELD score is now widely used in the prioritization of liver transplantation candidates in many countries. The score range is usually between 6 ( low risk ) and 40 ( high risk ).	1, 2, 3, and 4 weeks
Changes in COSSH-ACLF II score from baseline	COSSH-ACLF II is a prognostic scoring system for hepatitis B virus -related acute-on-chronic liver failure（HBV-ACLF）. COSSH-ACLF IIs can significantly divide ACLF patients into three risk groups based on two cutoff values of 7.4 and 8.4 : low-risk group ( < 7.4 points ), medium-risk group ( 7.4-8.4 points ) and high-risk group ( ≥ 8.4 points ).	1, 2, 3, and 4 weeks
Adsorption rates of various cytokines	Adsorption rates of various cytokines (including pro-inflammatory and anti-inflammatory cytokines) after each treatment	Day1
Adsorption rates of lactate	Adsorption rates of lactate after each treatment	Day1

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 17, 2024
• First Posted (Actual): August 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Digestive System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Liver Diseases; Liver Failure; Hepatic Insufficiency; Liver Failure, Acute; Pathological Conditions, Signs and Symptoms; Sepsis; Acute-On-Chronic Liver Failure; Therapeutics; Surgical Procedures, Operative; Biological Therapy; Blood Component Removal; Blood Transfusion; Plasmapheresis; Sorption Detoxification; Extracorporeal Circulation; Plasma Exchange
• Other Study ID Numbers: PL18

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 pliang@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