Source: DGNews  |  Posted 2 years ago

By Cheryl Lathrop

BOSTON -- November 2, 2009 -- Rifaximin protects patients with cirrhosis
against hepatic encephalopathy breakthrough -- even when rifaximin-naïve
patients were added to the trial, according to data from a large maintenance
study presented at the Liver Meeting 2009, the 60th Annual Meeting of the
American Association for the Study of Liver Diseases (AASLD).

In a previous randomised, double-blind, controlled trial of rifaximin 550 mg
twice daily versus placebo, 299 patients were enrolled from 70 centres in the
United States, Canada, and Russia. Rifaximin significantly reduced the risk of
breakthrough hepatic encephalopathy by 58% (P < .0001) and the risk
of hospitalisation related to hepatic encephalopathy by 50% (P =
.0129) over 6 months in patients with cirrhosis.

The open-label maintenance (OLM) trial was a long-term study of rollover
patients from the original trial (n = 152), as well as new rifaximin-naïve
patients (n = 115). A total of 267 patients were enrolled from 56 centres in
the United States, Canada, and Russia; treatment was again rifaximin 550 mg
twice daily. Fred Poordad, Liver Disease and Transplant Center, Cedars-Sinai
Medical Center, Los Angeles, California, and colleagues reported findings from
the OLM study here at a poster session on October 31.

Key inclusion criteria for new nonrollover patients was at least 1 verifiable
episode of hepatic encephalopathy associated with cirrhosis or portal
hypertension equivalent to a Conn score of 2 or more within 12 months of
screening. Exclusion criteria included daily prophylactic antibiotic therapy.
Patients were mostly white, fairly evenly divided between male and female, and
had a mean age of about 57 years.

For the placebo patients who crossed over to the OLM study, comparing their
experience in the original trial with their rifaximin experience in the OLM
study (analysing the time to first breakthrough of an overt hepatic
encephalopathy episode) demonstrated a significant protective effect for
rifaximin (hazard ratio [HR] = 0.302; 95% confidence interval [CI],
0.166-0.549; P < .0001). For the rifaximin patients in the original
trial who continued in the OLM study, the protective effect of rifaximin was
durable; the incidence of breakthrough episodes was lower than that for the
original placebo patients (HR = 0.08; 95% CI, 0.04-0.15; P < .0001).

In the original trial, the overall incidence of adverse events, the incidence
of drug-related adverse events, and serious adverse events were similar between
the rifaximin and placebo arm. Most deaths were related to advanced liver
disease, and not to the study drug. “The OLM trial is still ongoing,” noted the
authors, “and, to date, the rates and spectrum of adverse events in patients on
rifaximin therapy during [the randomised controlled trial] and OLM is similar
to those in [the original] placebo patients.”

Presentation title: The Protective Effect of Rifaximin (1100 mg daily)
From Hepatic Encephalopathy Observed in a Double-Blind Placebo Controlled Study
Is Substantiated and Durable Over the Long Term. Abstract 305