Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study.

Abstract

BACKGROUND & AIMS:

In acute liver failure (ALF), high blood ammonia levels have been documented that correlate with mortality and complications. L-ornithine L-aspartate (LOLA) reduces ammonia levels by increasing hepatic ammonia disposal and its peripheral metabolism. Present study evaluated efficacy and ammonia lowering effect of LOLA in ALF.

METHODS:

This study was placebo-controlled and blinded. We randomized 201 patients with ALF between January 2005 and October 2007 to either placebo or LOLA infusions (30 g daily) for 3 days. Arterial ammonia was measured at baseline and daily for 6 days. The primary end point was improvement in survival. The study followed CONSORT guidelines and was registered at the ClinicalTrials.gov (Identifier: NCT00470314).

RESULTS:

There was no reduction in mortality with LOLA treatment (mortality: 33.3% in placebo and 42.4% in LOLA; relative risk of death 1.27; 95% CI: 0.88-1.85; P = .204). By multivariate analysis, ammonia levels were an independent predictor of survival. There was significant decrease in ammonia levels in both groups with time (P < .001), but the levels of ammonia between the randomized groups at any time point, either during the 72 hours of LOLA infusion or during the follow-up were similar (P = .492). There was no difference between the 2 groups in the improvement in encephalopathy grade (P = .418), consciousness recovery time (P = .347), survival time (P = .612), or complications like seizures (P = .058) and renal failure (P = .615). The fetal outcome was also similar (P = .172). No adverse drug effect was noted.

CONCLUSIONS:

LOLA infusion did not lower the ammonia or improved survival in ALF.

• Authors: Subrat Kumar Acharya, Vikram Bhatia, Vishnubhatla Sreenivas, Shankar Khanal, Subrat Kumar Panda
• Journal: Gastroenterology (Gastroenterology) Vol. 136 Issue 7 Pg. 2159-68 (Jun 2009) ISSN: 1528-0012 [Electronic] United States
• PMID: 19505424 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Dipeptides
• ornithylaspartate

Topics

• Adult
• Dipeptides (administration & dosage)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Hyperammonemia (diagnosis, drug therapy)
• Kaplan-Meier Estimate
• Liver Failure, Acute (diagnosis, drug therapy, mortality)
• Male
• Probability
• Prospective Studies
• Reference Values
• Risk Assessment
• Statistics, Nonparametric
• Survival Analysis
• Treatment Outcome