Efficacy of L-Ornithine L-Aspartate in Acute Hepatic Encephalopathy.

Centro Regional para el Estudio de las Enfermedades Digestivas

Status and phase: Completed; Phase 4

Conditions: Hepatic Encephalopathy

Treatments: Drug: Lactose; Drug: L-ornithine-L-aspartate

Study type: Interventional

Funder types: Other

Identifiers

NCT01041755

MI09-002

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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30 participants in 2 patient groups

Intravenous infusion of L- Ornithine L- Aspartate

Experimental group

Description:

a) 20 g L-ornithine-L-aspartate

Treatment:

Drug: L-ornithine-L-aspartate

Lactose enemas

Active Comparator group

Description:

b) 20% Lactose enemas

Treatment:

Drug: Lactose