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NCT Number: NCT01041755

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

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.

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Key information

Conditions

Hepatic Encephalopathy Brain Diseases Brain Diseases, Metabolic Central Nervous System Diseases Digestive System Diseases Fibrosis Hepatic Insufficiency Liver Diseases Liver Failure Metabolic Diseases Nervous System Diseases Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Hospital Universitario "José Eleuterio González"

Monterrey, Nuevo León, 64460, Mexico

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

L-ornithine-L-aspartate

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.

Other names: LOLA

lactose

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.

Primary outcomes

  1. Improvement of at least one grade in mental state based on the West Haven Criteria

    Time frame: 72 hours

    Improvement was assessed at 0, 24, 48 and 72 hours. The mental state was scored from trivial lack of awareness to deep coma from grade 1 to grade 4.

Secondary outcomes

  1. Improvement of at least one grade in mental state assessed by the Glasgow Coma Scale

    Time frame: 72 hours

    Improvement was assessed at 0, 24, 48 and 72 hours. The Glasgow Coma Scale assesses three aspects of responsiveness: eye-opening, motor, and verbal responses. The eye-opening was quantified from 1 to 4 points, the motor response from 1 to 6 points and the verbal response from 1 to 5 points.

  2. Improvement of at least one grade in mental state assessed by the Clinical Hepatic Encephalopathy Staging Scale (CHESS)

    Time frame: 72 hours

    Improvement was assessed at 0, 24, 48 and 72 hours. The CHESS scale has 9 dichotomous questions that assess mental state, intellectual function, behavior, verbal and motor response and orientation. It was quantified from 0 to 9 points.

  3. Improvement of asterixis grade

    Time frame: 72 hours

    Improvement was assessed at 0, 24, 48 and 72 hours. Asterixis was graded as follows: Grade 0 = without flapping motion, Grade 1 ≤ 5 flaps per minute, Grade 2 = 6 to 10 flaps per minute, Grade 3 = 11 to 20 flaps per minute and Grade 4, continuous flap or patient in coma unable to maintain wrist dorsiflexion. Asterixis grade was evaluated at 0. 24, 48 and 72 hours.

  4. Improvement in electroencephalographic tracing grade

    Time frame: 72 hours

    Improvement was assessed at 0 and 72 hours. EEG tracing was graduated from 0 to 4: Grade 0 = normal alpha rhythm, Grade 1 =7 to 8 cycles per second, Grade 2= 5 to 6 cycles per second, Grade 3 = 3 to 4.5 cycles per second and Grade 4 < than 3 cycles per second or delta rhythm. EEG was assessed at 0 and 72 hours.

  5. Improvement in serum ammonia

    Time frame: 72 hours

    Ammonia determination was performed at 0, 24, 48 and 72 hours.

  6. Improvement in Number connection tests

    Time frame: 72 hours

    The mental state of the patients included in the study did not allow them to perform the number connection test, therefore, they were all assigned to the worst score (Grade 4)

  7. Improvement in Portosystemic Encephalopathy Index.

    Time frame: 72 hours

    Improvement was assessed at 0 and 72 hours. The PSE Index was calculated by multiplying the grade of mental state by a factor of 3; and the grades of asterixis, number connection tests, serum ammonia and EEG were multiplied times a factor of 1. The results were divided by the maximal possible PSE sum.

Sponsors and collaborators

Lead sponsor

Centro Regional para el Estudio de las Enfermedades Digestivas

Other

Collaborators

  • MERZ PHARMA

Registry information

Official study title

The Infusion of L-Ornithine L-aspart is as Effective as Nonabsorbable Disaccharides in the Management of Acute Hepatic Encephalopathy.

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Jan 1, 2010
Registry last updated
May 10, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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