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

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute-On-Chronic Liver Failure
• Intervention / Treatment: Device: HA 330-II; Drug: Standard medical treatment (SMT)

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 Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Telangana
    • Hyderabad, Telangana, India, 500032
      • Recruiting
      • Asian Institute of Gastroenterology
      • Contact: Mithun Sharma, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hemoperfusion treatment with 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.	Device: HA 330-II; One unit for 2-4 hours treatment, for 3 consecutive days; Drug: 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.
Active Comparator: 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.	Drug: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Asian Institute of Gastroenterology, India

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2019
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: January 17, 2020
• First Submitted That Met QC Criteria: January 24, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): January 28, 2020
• Last Update Submitted That Met QC Criteria: January 24, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• 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: AIG-G/ALFLD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No