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]
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