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.
|Hepatic Encephalopathy||Drug: L-ornithine-L-aspartate Drug: Lactose||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Infusion of L-Ornithine L-aspart is as Effective as Nonabsorbable Disaccharides in the Management of Acute Hepatic Encephalopathy.|
- Sustained improvement of at least one grade in mental state based on the West Haven criteria [ Time Frame: 48 hours ]
- Severity of hepatic encephalopathy assessed by the West Haven criteria [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ]
- Severity of hepatic encephalopathy assessed by the Glasgow Coma Scale [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ]
- Severity of hepatic encephalopathy assessed by the Clinical Hepatic Encephalopathy Staging Scale (CHESS) [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ]
- Decrease in venous ammonia levels [ Time Frame: before intervention, 24, 48, and 72 hours after intervention ]
- Improvement in electroencephalographic tracing [ Time Frame: before intervention and 72 hours after intervention ]
|Study Start Date:||December 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Experimental: Intravenous infusion of L- Ornithine L- Aspartate
a) 20 g 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
Active Comparator: Lactose enemas
b) 20% Lactose enemas
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01041755
|Hospital Universitario "José Eleuterio González"|
|Monterrey, Nuevo León, Mexico, 64460|
|Study Director:||Francisco J Bosques, MD, PhD||Centro Regional para el Estudio de las Enfermedades Digestivas|
|Principal Investigator:||Claudia Isabel Blanco Vela, MD||Hospital Juárez de México|