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evident
Original paper
2010NEJMGastroenterology/Hepatology

Rifaximin HE trial

Rifaximin treatment in hepatic encephalopathy

RCTHepatic encephalopathy

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Overview

In remission from recurrent HE, rifaximin 550 mg twice daily reduced breakthrough HE over 6 months versus placebo.

Clinical takeaway

Use rifaximin to prevent recurrent hepatic encephalopathy. Most patients were already on lactulose, so this is largely add-on prevention, not treatment of an acute episode.

Key result

Rifaximin reduced breakthrough HE versus placebo (HR 0.42, 95% CI 0.28-0.64; P<0.001); events occurred in 22.1% versus 45.9%.

Practice impact

Add rifaximin 550 mg twice daily to prevent recurrent HE, usually on top of lactulose.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

299

Follow-up

6 months.

Geography

Not listed

Clinical question

Does rifaximin prevent breakthrough hepatic encephalopathy in patients in remission from recurrent HE?

Population

  • 299 patients in remission from recurrent hepatic encephalopathy due to chronic liver disease (140 assigned to rifaximin, 159 to placebo).

Intervention

Rifaximin 550 mg twice daily for 6 months.

Comparator

Placebo for 6 months. More than 90% of patients received concomitant lactulose.

Primary outcome

Time to the first breakthrough episode of hepatic encephalopathy.

Rifaximin reduced the risk of breakthrough hepatic encephalopathy over 6 months compared with placebo.

Hazard ratio / 0.42 / 95% CI 0.28-0.64 / p<0.001

Key results

  • Rifaximin reduced the risk of a hepatic encephalopathy episode over 6 months versus placebo (HR 0.42, 95% CI 0.28-0.64; P<0.001).
  • A breakthrough episode occurred in 22.1% with rifaximin versus 45.9% with placebo.
  • The key secondary end point, time to first hospitalization involving hepatic encephalopathy, also favored rifaximin: 13.6% versus 22.6% were hospitalized (HR 0.50, 95% CI 0.29-0.87; P=0.01).

Harms

  • The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events.

Clinical Use

Practice impact

  • Use rifaximin 550 mg twice daily to maintain remission after recurrent HE, typically with lactulose.

Applicability

  • Most applicable to patients already in remission from recurrent hepatic encephalopathy due to chronic liver disease. More than 90% were taking lactulose.

Limitations

  • This is a prevention trial in patients already in remission, not a trial of rifaximin for an acute HE episode.
  • Assignment was unbalanced (140 rifaximin vs 159 placebo) among 299 randomized patients.

Common misinterpretations

  • This does not establish rifaximin as monotherapy; most patients received concomitant lactulose.
  • Efficacy for acute HE is not what this trial tested.

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Citation

Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081. doi:10.1056/NEJMoa0907893

Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo.