Clinical trial NCT01041755: Efficacy of L-Ornithine L-Aspartate in Acute Hepatic Encephalopathy.
Official title: The Infusion of L-Ornithine L-aspart is as Effective as Nonabsorbable Disaccharides in the Management of Acute Hepatic Encephalopathy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatic Encephalopathy
Keywords: Encephalopathy
Cirrhosis
Lead sponsor: Centro Regional para el Estudio de las Enfermedades Digestivas
Sponsor class: OTHER
Collaborators: name: MERZ PHARMA
First posted: 2010-01-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hepatic encephalopathy is caused by the effects on the brain of substances that under normal circumstances are efficiently metabolized in the liver. The hyperammonemia is the main factor responsible for the development of hepatic encephalopathy. In patients with cirrhosis, the reduction in hepatocellular function and generation of portosystemic shunts contribute to increase serum ammonium. The current therapeutic approaches, are aimed at reducing blood ammonium levels.

Administration of the non-absorbable disaccharides, have become standard treatment of hepatic encephalopathy.There are no adequate clinical trials comparing the efficacy of L-Ornithine-L-Aspartate (LOLA) infusion against lactose enemas in the treatment of acute hepatic encephalopathy.

Detailed description: The main impact of hepatic encephalopathy in patients with cirrhosis is not related to costs, but its association with decreased survival and quality of life and should therefore clearly established the effectiveness of therapeutic interventions used in this disorder.

At the end of the nineteenth century to the ammonium was identified as the main agent responsible for the development of the syndrome of hepatic encephalopathy. Since then, reduced nitrogen compounds from the intestine are considered the main therapeutic measure. On this conceptual base, nonabsorbable disaccharides are the first line therapy in hepatic encephalopathy.

Current knowledge indicates that other organs such as muscle, brain and kidney are involved in the generation of ammonium, which has set the pace for the development of new treatments, able to act systemically in metabolism and elimination of ammonia . L-ornithine L-aspartate (LOLA) lowers ammonium concentrations in animal and humans models with hyperammonemia. There are no adequate clinical trials comparing the efficacy of LOLA infusion against lactose enemas in the treatment of acute hepatic encephalopathy.

Eligibility criteria: Inclusion Criteria:

* Patients with cirrhosis of any etiology, diagnosed by ultrasound,clinical and / or histologic criteria
* Patients over 18 years and under 75
* Patients with hepatic encephalopathy grade 3-4 according to the criteria of West Haven
* Patients with hyperammonemia \>10 µmol/l

Exclusion Criteria:

* Evidence of neurological or psychiatric illness
* Use of drugs affecting the central nervous system
* Withdrawal Syndrome
* Anorectal disease that interferes with the administration of enemas

Primary outcomes:
measure: Improvement of at least one grade in mental state based on the West Haven Criteria
timeFrame: 72 hours
Secondary outcomes:
measure: Improvement of at least one grade in mental state assessed by the Glasgow Coma Scale
timeFrame: 72 hours
measure: Improvement of at least one grade in mental state assessed by the Clinical Hepatic Encephalopathy Staging Scale (CHESS)
timeFrame: 72 hours
measure: Improvement of asterixis grade
timeFrame: 72 hours
measure: Improvement in electroencephalographic tracing grade
timeFrame: 72 hours
measure: Improvement in serum ammonia
timeFrame: 72 hours
measure: Improvement in Number connection tests
timeFrame: 72 hours
measure: Improvement in Portosystemic Encephalopathy Index.
timeFrame: 72 hours
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Hospital Universitario "José Eleuterio González"
state: Nuevo León
Study officials:
affiliation: Centro Regional para el Estudio de las Enfermedades Digestivas
name: Francisco J Bosques, MD, PhD
role: STUDY_DIRECTOR
affiliation: Hospital Juárez de México
name: Claudia Isabel Blanco Vela, MD
role: PRINCIPAL_INVESTIGATOR
References: