Ornithine phenylacetate no better than placebo for cirrhosis, hepatic encephalopathy

In the treatment of patients with cirrhosis and hepatic encephalopathy (HE), the ammonia scavenger ornithine phenylacetate is safe and similar to placebo in terms of time to clinical improvement, according to data from a phase IIb trial.

The trial randomized 231 patients to treatment with placebo (n=115) or OP (n=116) at 10, 15, or 20 g daily based on the severity of liver disease. All patients also received standard of care (eg, lactulose to achieve 2–3 bowel movements with or without rifaximin, in accordance with guidelines).

Patient characteristics at baseline were generally similar in the two groups. The median ammonia levels for patients who received any OP (n=113) or placebo (n=111) were 86.9 μmol/L (range, 23.4–242.7) and 85.9 μmol/L (range, 6.2–398.8), respectively.

The primary endpoint of time to confirmed clinical response (ie, regression from HE staging tool [HEST] stages 3/4 at baseline to stage 2 or from HEST stage 2 to stages 0/1, based on ammonia levels measured at local laboratories) did not significantly differ across the OP groups and the placebo group (p=0.129).

On the other hand, analyses of central laboratory–confirmed increases in levels of ammonia at baseline (n=201) revealed that clinical improvement in HE occurred a median of 21 hours sooner with OP than with placebo.

In terms of safety, the percentages of patients with any specific adverse event were similar across the treatment groups. Serious adverse events were documented in 25 percent of patients who received OP and in 29 percent of those who received placebo (p=0.552).

The findings suggest that OP may be beneficial to patients with HE grades of 2 or higher and ammonia levels greater than the upper limit of normal confirmed by a central laboratory.