Clinical trial NCT04243655: Use of HA 330-II for Hemofiltration in Patients With ALF as a Bridge to Liver Transplantation .
Official title: Use of HA 330-II for Hemofiltration in Patients With Acute Liver Failure as a Bridge to Liver Transplantation: Clinical Evaluation Protocol.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute-On-Chronic Liver Failure
Lead sponsor: Asian Institute of Gastroenterology, India
Sponsor class: OTHER
First posted: 2020-01-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with standard medical treatment (SMT) as per patients requirement.
Primary purpose: TREATMENT

Brief summary: ALF (ALF) is defined by three criteria: (1) rapid development of hepatocellular dysfunction (jaundice, coagulopathy), (2) hepatic encephalopathy, and (3) absence of a prior history of liver disease.

Interval between onset of acute hepatic injury (jaundice) and onset of liver failure (encephalopathy with or without coagulopathy) in such patients (icterus-encephalopathy interval; IEI) has been described to be between 4 weeks (Indian definition) to 24 weeks (AASLD-ALF study group). Further, due to the diverse natural course, ALF has been sub-classified as hyperacute (IEI ≤ 7 day), acute (IEI ≤ 4 weeks) and sub-acute ALF (IEI ≥ 5 week to ≤12 weeks) by British authors.

Detailed description: Since the 1960s, Liver Transplantation (LT) has emerged as a cornerstone intervention to cure liver failure. Mortality in patients with liver failure who cannot be rescued with Liver Transplantation remains high despite improvements in supportive care.

Artificial Liver Support System (ALSS) in ALF aim to remove excess inflammatory cytokines and attenuate inflammatory response, to remove albumin-bound and water-soluble toxins, to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. ALSS may also provide benefit in instances where LT is contraindicated.

The following beneficial effects have been documented with ALSS in ALF patients: improvement of jaundice, amelioration of hemodynamic instability, improvement of hepatic encephalopathy, SOFA score and survival.

HA 330-II is a broad-spectrum adsorbent made of neutral macroporous resin, removes toxins such as Inflammatory mediators (IL-1, IL-6, IL-8 \& TNF-α) along with hepatic toxins such as phenol, mercaptan, aromatic amino acids, false neurotransmitters and indirectly ammonia by improving liver function recovery. However, this indirect ammonia removal with HA 330-II is insignificant. By removing excess inflammatory cytokines and attenuating uncontrolled immune response, HA 330-II prevents worsening of encephalopathy, improves liver function recovery and improves prognosis.

Eligibility criteria: Inclusion Criteria:

• Acute Liver Failure patients with SIRS and Hepatic Encephalopathy, without hyperbilirubinemia.

Exclusion Criteria:

* Patients with age less than 18 years or more than 65 years
* Extremely moribund patients with an expected life expectancy of less than 24 hours or with poor prognosis
* With poor blood clotting function and PTA \<30%.
* Active Bleed
* Chronic heart, lung or kidney disease
* Malignant tumors including liver cancer
* Past history of organ transplantation

Primary outcomes:
measure: Efficacy of HA 330-II to prolong liver-transplantation free survival.
timeFrame: Up to 30 Days
Secondary outcomes:
measure: Change in Systemic inflammatory response syndrome (SIRS) score.
timeFrame: Up to 7 Days, post hemofiltration
measure: Change in Acute Physiology and Chronic Health Evaluation (APACHE-II) score.
timeFrame: Up to 7 Days, post hemofiltration
measure: Change in sequential organ failure assessment (SOFA) score.
timeFrame: Up to 7 Days, post hemofiltration
measure: Change in chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score.
timeFrame: Up to 7 Days, post hemofiltration
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: Asian Institute Of Gastroenterology
state: Telangana
Study officials:
affiliation: AIG Hospitals
name: Mithun Sharma
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology. 2000 Oct;32(4 Pt 1):734-9. doi: 10.1053/jhep.2000.17687.
citation: Lee KC, Stadlbauer V, Jalan R. Extracorporeal liver support devices for listed patients. Liver Transpl. 2016 Jun;22(6):839-48. doi: 10.1002/lt.24396.
citation: Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, Triantafyllou E, Bernal W, Auzinger G, Shawcross D, Eefsen M, Bjerring PN, Clemmesen JO, Hockerstedt K, Frederiksen HJ, Hansen BA, Antoniades CG, Wendon J. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol. 2016 Jan;64(1):69-78. doi: 10.1016/j.jhep.2015.08.018. Epub 2015 Aug 29.