Immediate-release rifaximin may prevent complications, boost recovery in cirrhotic patients with OHE

Rifaximin soluble solid dispersion (SSD) immediate-release (IR) tablet has the potential to reduce hospitalization in patients with cirrhosis and promote the resolution of overt hepatic encephalopathy (OHE) during hospitalization, according to analyses of two phase II trials.

The first trial randomized 516 outpatients with early decompensated cirrhosis to placebo or rifaximin SSD once-nightly (IR 40 or 80 mg, sustained extended-release [SER] 40 or 80 mg, or IR 80 mg plus SER 80 mg) for 24 weeks.

The second trial consisted of 71 inpatients with OHE who were randomized to treatment with lactulose plus placebo or rifaximin SSD (IR 40 mg once or twice daily [qd/bid] or SER 80 mg qd/bid) for ≤14 days.

The primary efficacy endpoint of time to cirrhosis complication-related hospitalization/all-cause mortality in trial 1 did not significantly differ between the placebo and active treatment groups. However, a post hoc analysis showed that the outcome was markedly improved among patients on IR 40 mg than among those on placebo (15.4 percent vs 27.7 percent; p=0.03).

In trial 2, the primary outcome of time to OHE resolution occurred sooner with rifaximin SSD IR 40 mg bid than with lactulose plus placebo (21.1 vs 62.7 hours; p=0.02). Trial was subsequently terminated.

Data from these phase II trials, which did not achieve their prespecified endpoints and may be considered negative, suggest that rifaximin SSD IR 40 mg may be useful in the treatment of patients with cirrhosis and OHE. The findings are considered hypothesis-generating and warrant further clinical development of this investigational rifaximin formulation in phase III trials.