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

Acute-On-Chronic Liver Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04243655
• Other study ID #: AIG-G/ALFLD
• Status: Recruiting
• Phase: Phase 4
• Start date: December 30, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: January 2020
• Source: Asian Institute of Gastroenterology, India
• Contact: Mithun Sharma, MD, DM
• Phone: 08790622655
• Email: drmithunsharma[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 31, 2020
• Est. primary completion date: October 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• End Stage Liver Disease
• Hepatic Insufficiency
• Liver Failure

Intervention

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.

Locations

Country	Name	City	State
India	Asian Institute Of Gastroenterology	Hyderabad	Telangana

Sponsors (1)

Lead Sponsor	Collaborator
Asian Institute of Gastroenterology, India

Country where clinical trial is conducted

India, 

References & Publications (3)

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. — View 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. Review. — View 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. — View Citation

Outcome

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