Use of HA 330-II for Hemofiltration in Patients With ALF as a Bridge to Liver Transplantation .

Phase 4

• Conditions: Acute-On-Chronic Liver Failure
• Interventions: Device: HA 330-II; Drug: Standard medical treatment (SMT)

• Registration Number: NCT04243655
• Lead Sponsor: Asian Institute of Gastroenterology, India

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.

Study Timeline

• Study Start: 2019-12-30
• Status Verified: 2020-01
• Study First Submitted: 2020-01-17
• Study First Submitted QC: 2020-01-24
• Last Update Submitted: 2020-01-24
• Study First Posted: 2020-01-28
• Last Update Posted: 2020-01-28
• Primary Completion: 2020-10
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hemoperfusion treatment with HA 330-II	HA 330-II	Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with SMT as per patients requirement.
Hemoperfusion treatment with HA 330-II	Standard medical treatment (SMT)	Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with SMT as per patients requirement.
Standard medical treatment (SMT)	Standard medical treatment (SMT)	SMT as per patients requirement- Management of cerebral edema/intracranial hypertension: prophylactic antibiotics, administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure, volume replacement and pressor support (noradrenaline, doubutamine, dopamine) as needed, NAC and correction of metabolic parameters.

Primary Outcome Measures

Name	Time	Method
Efficacy of HA 330-II to prolong liver-transplantation free survival.	Up to 30 Days	The length of survival time after first hemofiltration treatment during the follow-up period.

Secondary Outcome Measures

Name	Time	Method
Change in Systemic inflammatory response syndrome (SIRS) score.	Up to 7 Days, post hemofiltration	To assess efficacy of treatment.
Change in chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score.	Up to 7 Days, post hemofiltration	To assess efficacy of treatment.
Change in Acute Physiology and Chronic Health Evaluation (APACHE-II) score.	Up to 7 Days, post hemofiltration	To assess efficacy of treatment.
Change in sequential organ failure assessment (SOFA) score.	Up to 7 Days, post hemofiltration	To assess efficacy of treatment.

Trial Locations

Locations (1)

Asian Institute Of Gastroenterology; 🇮🇳 Hyderabad, Telangana, India