The Effects of Double Plasma Molecular Adsorption System in Acute on Chronic Liver Failure Patients

Acute liver failure patients posed high mortality rate despite receiving standard therapy. The severity and mortality even higher in patients with underlying liver disease. Acute liver failure cause hyperinflammatory response in early stage and immunoparalysis in later stage. The surge of proinflammatory cytokines leads to multiorgan failure and more liver injury. Subsequent immunoparalysis may lead to lethal secondary infections.

Liver support system had been used in acute and acute ontop chronic liver disease for last several decades. Double plasma molecular adsorption system (DPMAS) is one of the promising non-biological liver support system that have been extensively investigated in acute ontop chronic liver failure from hepatits B viral. DPMAS circuit consist of BS330 (bilirubin adsorber) and HA330 (Cytokines adsorber). Thus, DPMAS can also remove various cytokines. The effect of DPMAS on immune function in these patients has not been explored.

Recent randomized controlled trial by Srisawat et al. demonstrated improvement of mHLA-DR in septic shock patients who received polymyxin B extracorporeal therapy compare to control arm. Since liver failure show change of immunological profile resemble to sepsis. Investigators proposed that removal of toxic liver toxins and lethal cytokines by DPMAS will improve immunological profiles in acute ontop chronic liver failure patients.

Investigators plan to conduct a randomized controlled trial in acute ontop chronic liver failure patients who admitted to intensive care unit. Investigators plan to compare the immunomodulatory effects of DPMAS with standard treatments.

Study Overview

• Status: Recruiting
• Conditions: Acute-On-Chronic Liver Failure; Acute on Chronic Hepatic Failure
• Intervention / Treatment: Device: DPMAS; Other: standard treatment

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Phatadon Sirivongrangson, MD; Phone Number: (+66)0852447788; Email: phatadon@hotmail.com

Study Locations

• Thailand
  • Bangkok, Thailand
    • Recruiting
    • King Chulalongkorn Memorial Hospital
    • Contact: Sasipha Tachaboon

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 or more
2. Diagnosis of Acute ontop chronic liver failure by Asian Pacific association for the study of the liver (APASL) criteria
3. Admitted to intensive care unit

Exclusion Criteria:

1. Pregnancy
2. Received steroid treatment
3. Expected dead within 24 hour
4. WBC < 500/mm3
5. Allergy to DPMAS
6. History of organ transplant
7. Terminal illness with do not resuscitation order

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: Intervention; Intervention group will receive DPMAS extracorporeal treatment one session per day for 3 consecutive days plus standard therapy. We plan to use blood flow rate of 100-120 ml/hour with filtration fraction for plasma separation of 25-30%. DPMAS circuit consist of Plasmaflo OP cartridge (Asahi Medical, Tokyo, Japan), Ion exchange resin hemoperfusion cartridge (BS330; Jafron, Zhuhai City, China), and Neutral adsorption resin hemoperfusion cartridge (HA330-II; Jafron, Zhuhai City, China) We do not use any anticoagulant.	Device: DPMAS; DPMAS circuit consist of Plasmaflo OP cartridge (Asahi Medical, Tokyo, Japan), Ion exchange resin hemoperfusion cartridge (BS330; Jafron, Zhuhai City, China), and Neutral adsorption resin hemoperfusion cartridge (HA330-II; Jafron, Zhuhai City, China); Other: standard treatment; standard treatment according to EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure 2017.
Active Comparator: Standard care; Standard treatment according to EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure 2017	Other: standard treatment; standard treatment according to EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure 2017.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mHLA-DR expression	mHLA-DR expression	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
survival rate	survival rate	28 days
Reduction of total bilirubin	Reduction of total bilirubin	7 days
hepatic encephalopathy grading	hepatic encephalopathy grading	28 days
subsequent bacterial infection	subsequent bacterial infection	28 days
CD11b expression	CD11b expression	7 days

Collaborators and Investigators

• Sponsor: Chulalongkorn University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Hemoperfusion; Acute-On-Chronic Liver Failure; Cytokine adsorbant therapy; HA-330
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure
• Other Study ID Numbers: IRB.216/64

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No