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

NCT ID: NCT01041755

Last Updated: 2021-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2011-06-30

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.

Conditions

Hepatic Encephalopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intravenous infusion of L- Ornithine L- Aspartate

a) 20 g L-ornithine-L-aspartate

Group Type: EXPERIMENTAL

L-ornithine-L-aspartate

Intervention Type: DRUG

a) Intravenous infusion of 20 g L-ornithine-L-aspartate (4 ampules of 10 mL each) in 250 mL sodium chloride solution administered daily in 4 hours for 3 consecutive days, plus the placebo b) Water enemas, 1000 mL of water and given as retention enema every 12 hours for 3 consecutive days.

Lactose enemas

b) 20% Lactose enemas

Group Type: ACTIVE_COMPARATOR

Lactose

Intervention Type: DRUG

a) 20% Lactose enemas, 200 g Lactose diluted with 700 mL of water and given as retention enema every 12 hours for 3 consecutive days, plus intravenous placebo b)250 mL sodium chloride solution, infusion for 4 hours for 3 consecutive days.

Interventions

L-ornithine-L-aspartate

a) Intravenous infusion of 20 g L-ornithine-L-aspartate (4 ampules of 10 mL each) in 250 mL sodium chloride solution administered daily in 4 hours for 3 consecutive days, plus the placebo b) Water enemas, 1000 mL of water and given as retention enema every 12 hours for 3 consecutive days.

Intervention Type: DRUG

Lactose

a) 20% Lactose enemas, 200 g Lactose diluted with 700 mL of water and given as retention enema every 12 hours for 3 consecutive days, plus intravenous placebo b)250 mL sodium chloride solution, infusion for 4 hours for 3 consecutive days.

Intervention Type: DRUG

Other Intervention Names

LOLA

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MERZ PHARMA

UNKNOWN

Sponsor Role: collaborator

Centro Regional para el Estudio de las Enfermedades Digestivas

OTHER

Sponsor Role: lead

Responsible Party

Dr. Claudia Isabel Blanco Vela

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francisco J Bosques, MD, PhD

Role: STUDY_DIRECTOR

Centro Regional para el Estudio de las Enfermedades Digestivas

Claudia Isabel Blanco Vela, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Juárez de México

Locations

Hospital Universitario "José Eleuterio González"

Monterrey, Nuevo León, Mexico

Countries

Mexico

Other Identifiers

MI09-002

Identifier Type: -

Identifier Source: org_study_id