Very Low-volume Plasma Exchange in ACLF
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-65
SponsorThird Affiliated Hospital, Sun Yat-Sen University
About this trial
This is a prospective, multicenter, open-label, non-inferiority, randomized controlled trial evaluating the efficacy and safety of very low plasma exchange (400 mL plasma + prothrombin complex concentrate) and plasma-free (prothrombin complex concentrate only) artificial liver support systems compared with standard low-volume plasma exchange (1000 mL plasma) in patients with acute-on-chronic liver failure (ACLF). A total of 840 eligible patients (COSSH grade 1-2) will be enrolled from 10 centers across China and randomly assigned in a 1:1:1 ratio to receive three sessions of treatment (every 2-3 days) combined with standard medical therapy. The primary endpoint is 28-day non-liver-transplant mortality, with a non-inferiority margin of 10%. Secondary endpoints include 90-day non-liver-transplant mortality, 90-day bridging to liver transplantation rate, changes in prognostic scores (COSSH-ACLF Ⅱ, MELD, CLIF-C ACLFs) from baseline at 2 weeks, and total plasma volume used during hospitalization. Safety outcomes include adverse events (bleeding, coagulation disorders, thrombosis, hypotension, infections, allergic reactions). The study aims to establish a plasma-sparing treatment strategy that reduces dependence on blood products while maintaining non-inferior efficacy. The trial is funded by the National Science and Technology Major Project of China and approved by the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University (Approval No.: 中大附三医伦RG2026-044-01; Approval Date: April 29, 2026). Enrollment is planned from May 2026 to October 2027, with follow-up completed by October 2028. Written informed consent will be obtained from all participants.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age between 18 and 65 years, inclusive.
Diagnosed with acute-on-chronic liver failure (ACLF) according to the Chinese Guidelines for the Diagnosis and Treatment of Liver Failure (2024), defined as: chronic liver disease (with or without cirrhosis), total bilirubin (TBil) ≥ 12 mg/dL (≥ 205.2 μmol/L) and international normalized ratio (INR) ≥ 1.5.
COSSH-ACLF grade 1 or 2.
Disqualifiers
Patients with malignant tumors.
Pregnant or lactating women.
Patients co-infected with HIV or other immunodeficiency diseases.
Patients with unstable cerebral or cardiovascular infarction, or history of organ transplantation.
Trial design
Design model
Parallel
Treatments tested in this trial
Double Plasma Molecular Adsorption System (DPMAS)
Other interventionDPMAS is performed using a hemoperfusion cartridge (HA330-II, Jafron, Zhuhai) and a plasma bilirubin adsorption column (BS330, Jafron, Zhuhai). Each session has an adsorption volume of 5000 mL with a duration of 2-3 hours. The procedure is performed via jugular or femoral vein catheterization, with heparin or nafamostat used for anticoagulation. All three arms receive DPMAS as the core artificial liver support treatment.
Low-volume plasma exchange
Other interventionThree session of plasma exchange with 1000 mL fresh frozen plasma is performed immediately after DPMAS.
Prothrombin Complex Concentrate (PCC)
DrugProthrombin complex concentrate (300-400 IU) is administered as an intravenous infusion immediately after completion of the artificial liver support system.
Standard Medical Therapy
Other interventionAll participants receive standard medical therapy for acute-on-chronic liver failure per the Chinese Guidelines for the Diagnosis and Treatment of Liver Failure (2024), including antiviral therapy (for HBV/HCV), anti-infective treatment, nutritional support, symptomatic treatment, and prevention/management of complications.
Very low-volume plasma exchange
Other interventionThree sessions of plasma exchange with 400 mL fresh frozen plasma is performed immediately after DPMAS.
Treatment groups
840 Participants
are divided into 3 treatment groupsGroup A: Standard Low-Volume Plasma Exchange (Control Group)Active comparator 3 interventions
Group B: Very Low-volume Plasma Exchange with Prothrombin Complex ConcentrateExperimental treatment 4 interventions
Group C: Plasma-Free DPMAS with Prothrombin Complex ConcentrateExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
28-Day Non-Liver-Transplant Mortality
The proportion of participants who die from any cause without liver transplantation within 28 days from enrollment. Survival status is assessed via inpatient monitor of telephone follow-up or outpatient visit.
Time frame
Day 28 post-enrollment (± 3 days)Secondary outcomes
1
90-Day Non-Liver-Transplant Mortality
The proportion of participants who die from any cause without liver transplantation within 90 days from enrollment.
Time frame
90 days after enrollment2
90-Day Bridging to Liver Transplantation Rate
The proportion of participants who undergo liver transplantation within 90 days from enrollment.
Time frame
90 days after enrollment3
Change in Prognostic Scores (COSSH-ACLF Ⅱ, MELD, CLIF-C ACLFs) from Baseline at 2 Weeks
Changes in three validated acute-on-chronic liver failure (ACLF) prognostic scoring systems at 2 weeks relative to baseline: Chinese Group on the Study of Severe Hepatitis B (COSSH)-ACLF Ⅱ (COSSH-ACLF Ⅱscore = 0.033 × age + 0.396 × ln (serum TBIL) (umol/L) + 1.649 × ln (PT-INR) + 0.576 × ln (serum BUN) (mmol/L) + 0.425 × ln (neutrophil) (10E9/L) + 0.457 × HE score (HE grade 0 = 1, grade 1 and 2 = 2, grade 3 and 4 = 3)), model for end-stage liver disease (MELD, MELD score= 3.78 × ln (serum TBIL) (mg/dL) + 11.20 × ln (PT-INR) + 9.57 × ln (serum creatinine) (mg/dL) + 6.43), and Chronic Liver Failure Consortium (CLIF-C) ACLFs (CLIF-C ACLFs score = 10 × (0.33 × CLIF-OFs + 0.04 × Age + 0.63 × ln(WBC)(10E9/L) - 2) ). Higher score means a worse outcome.
Time frame
Baseline (Day -2 to 0) to Day 14 post-enrollment (± 3 days)4
Total Plasma Volume Used During Hospitalization
Cumulative total volume of fresh frozen plasma (mL) used from enrollment to discharge, extracted from medical records.
Time frame
Through study completion, an average of 3 monthsLocations
Sponsors and contacts
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Source ClinicalTrials.gov
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