Efficacy of Albumin for Acute Encephalopathy in Patients With Cirrhosis (ALFAE)

Effects of the Administration of Albumin in Patients With Cirrhosis and Acute Hepatic Encephalopathy.

The purpose of this study is to determine whether the administration of albumin in addition to the standard care is effective in the treatment of an episode of hepatic encephalopathy in patients with cirrhosis.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: Albumin; Drug: Sodium chloride 0.9%

Detailed Description

Hepatic encephalopathy is a frequent complication of cirrhosis that is usually associated with poor prognosis. The most common presentation is an acute episode of hepatic encephalopathy precipitated by factors that increase the exposure of the brain to ammonia. Current therapies are based on measures that decrease plasma ammonia and counteract the effect of factors such as infection or electrolyte's disturbances. Brain edema and abnormalities of cerebral blood flow appear to be important. Part of the impairment of astrocyte function could be related to an increase of oxidative stress injury.

In patients with cirrhosis and hepatic encephalopathy, the concentration of albumin in plasma is usually low. Administration of human albumin in patients with hepatorenal syndrome and spontaneous bacterial peritonitis has a major impact on the prognosis of these complications. Albumin prevents circulatory dysfunction and renal failure. The mechanisms of action may include the maintenance of oncotic pressure and a scavenger effect of toxic substances present in blood. Albumin has also shown beneficial effects in neurological injury secondary to stroke, probably in relation to this scavenger effect.

The administration of intravenous albumin to patients with hepatic encephalopathy may have beneficial effects on the course of encephalopathy.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Hospital de Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clínic
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona
    • Sabadell, Barcelona, Spain
      • Parc Taulí

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cirrhosis of the liver
• Hepatic encephalopathy stage>1
• Completion of a standardized protocol to investigate precipitating factors
• Informed consent by next of keen

Exclusion Criteria:

• Pregnancy
• Terminal liver disease (advanced liver disease and performance status 3-4 prior to the episode of acute encephalopathy)
• Need of advanced life support (mechanical ventilation, ionotropic support, dialysis)
• Need of albumin administration (e.g. bacterial spontaneous peritonitis)
• Contraindication for albumin administration (e.g. cardiac failure)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline	Drug: Sodium chloride 0.9%; Day 0: 400-600 ml. Day 2: 200-400 ml.
Active Comparator: Albumin	Drug: Albumin; Albumin 20%. Day 0: 400-600 ml. Day 2: 200-400 ml.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients without hepatic encephalopathy	Day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Severity of encephalopathy assessed by CHESS and West-Haven	Admission to the hospital (up to day 14)

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Publications and helpful links

General Publications

• Simon-Talero M, Garcia-Martinez R, Torrens M, Augustin S, Gomez S, Pereira G, Guevara M, Gines P, Soriano G, Roman E, Sanchez-Delgado J, Ferrer R, Nieto JC, Sunye P, Fuentes I, Esteban R, Cordoba J. Effects of intravenous albumin in patients with cirrhosis and episodic hepatic encephalopathy: a randomized double-blind study. J Hepatol. 2013 Dec;59(6):1184-92. doi: 10.1016/j.jhep.2013.07.020. Epub 2013 Jul 19.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: April 22, 2009
• First Submitted That Met QC Criteria: April 22, 2009
• First Posted (Estimate): April 23, 2009

Study Record Updates

• Last Update Posted (Estimate): December 17, 2012
• Last Update Submitted That Met QC Criteria: December 14, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Cirrhosis; Albumin; Hepatic encephalopathy
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Fibrosis; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: ALFAE; 2008-003376-21 (EudraCT Number); PI07 - 0641 (Other Grant/Funding Number: FIS (Instituto de Salud Carlos III))