リファキシミン550mgを１日２回投与（140名）と、プラセボ（159名）で６ヶ月間のランダム化二重盲検比較試験。第一のアウトカムは、初回の肝性脳症症状。リファキシミンが、肝性脳症のリスクを減少（ハザード比0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001）。肝性脳症の発症は、リファキシミン投与群で22.1%、プラセボ群で45.9%。そのうち入院率は、リファキシミン投与群13.6%、プラセボ群で22.6%（ハザード比 0.50 (95% CI, 0.29 to 0.87; P=0.01)）。90%以上の患者が、ラクツロースの治療を行っていた。副作用は同等。
Rifaximin treatment in hepatic encephalopathy.
N Engl J Med. 2010 Mar 25;362(12):1071-81.
Background Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established.
Methods In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy.
Results Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P=0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events.
Conclusions Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy.