Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study.
OBJECTIVE
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.
Acharya
Subrat Kumar
SK
Department of Gastroenterology, All India Institute of Medical Sciences (AIIMS), New Delhi, India. subratacharya2004@yahoo.com
Bhatia
Vikram
V
Sreenivas
Vishnubhatla
V
Khanal
Shankar
S
Panda
Subrat Kumar
SK
D000328:Adult; D004151:Dipeptides / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D022124:Hyperammonemia / Q000175:diagnosis / Q000188:drug therapy*; D053208:Kaplan-Meier Estimate; D017114:Liver Failure, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
D004151:Dipeptides; C002939:ornithylaspartate