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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Centro Regional para el Estudio de las Enfermedades Digestivas.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Centro Regional para el Estudio de las Enfermedades Digestivas
ClinicalTrials.gov Identifier:
NCT01041755
First received: December 31, 2009
Last updated: June 21, 2011
Last verified: June 2011

December 31, 2009
June 21, 2011
December 2009
December 2011   (final data collection date for primary outcome measure)
Sustained improvement of at least one grade in mental state based on the West Haven criteria [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01041755 on ClinicalTrials.gov Archive Site
  • Severity of hepatic encephalopathy assessed by the West Haven criteria [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ] [ Designated as safety issue: No ]
  • Severity of hepatic encephalopathy assessed by the Glasgow Coma Scale [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ] [ Designated as safety issue: No ]
  • Severity of hepatic encephalopathy assessed by the Clinical Hepatic Encephalopathy Staging Scale (CHESS) [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ] [ Designated as safety issue: No ]
  • Decrease in venous ammonia levels [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ] [ Designated as safety issue: No ]
  • Improvement in electroencephalographic tracing [ Time Frame: before intervention and 72 hours after intervention ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Efficacy of L-Ornithine L-Aspartate in Acute Hepatic Encephalopathy.
The Infusion of L-Ornithine L-aspart is as Effective as Nonabsorbable Disaccharides in the Management of 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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hepatic Encephalopathy
  • Drug: 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.
    Other Name: LOLA
  • 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.
    Other Name: Lactose
  • Experimental: Intravenous infusion of L- Ornithine L- Aspartate
    Intervention: Drug: L-ornithine-L-aspartate
  • Active Comparator: Lactose enemas
    Intervention: Drug: Lactose
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
56
March 2012
December 2011   (final data collection date for primary outcome measure)

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 >35 µmol/l

Exclusion Criteria:

  • Evidence of other neurological or psychiatric abnormality
  • Renal failure (serum creatinine greater than 3 mg / dL)
  • Use of drugs affecting the central nervous system
  • Withdrawal Syndrome
Both
18 Years to 75 Years
No
Contact: Claudia I Blanco, MD +52 81 83333664 c_i_b_v@hotmail.com
Contact: Francisco J Bosques, MD, PhD +52 81 83333664 fbosques58@hotmail.com
Mexico
 
NCT01041755
MI09-002
No
Claudia Isabel Blanco Vela MD, Centro Regional para el Estudio de las Enfermedades Digestivas, Hospital Universitario "Dr. José Eleuterio González"
Centro Regional para el Estudio de las Enfermedades Digestivas
Not Provided
Study Director: Francisco J Bosques, MD, PhD Centro Regional para el Estudio de las Enfermedades Digestivas
Centro Regional para el Estudio de las Enfermedades Digestivas
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP