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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Use of HA 330-II for Hemofiltration in Patients With Acute Liver Failure as a Bridge to Liver Transplantation: Clinical Evaluation Protocol.

Conditions
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Acute-On-Chronic Liver Failure

Intervention / Treatment
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* Device: HA 330-II
* Drug: Standard medical treatment (SMT)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemoperfusion treatment with HA 330-II<br>Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with SMT as per patients requirement. | Device: HA 330-II<br>* One unit for 2-4 hours treatment, for 3 consecutive days<br>Drug: Standard medical treatment (SMT)<br>* 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.<br>|
| Active Comparator: Standard medical treatment (SMT)<br>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. | Drug: Standard medical treatment (SMT)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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