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.