1Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. Electronic address: email@example.com.
2Virginia Commonwealth University, Richmond, Virginia, USA.
3University of California San Francisco (UCSF), San Francisco, California, USA.
4The Texas Liver Institute/University of Texas Health Science Center, San Antonio, TX, USA.
5University of California San Francisco (UCSF) Fresno MEP, Fresno, California, USA.
6California Pacific Medical Center, San Francisco, California.
7Salix Pharmaceuticals, Inc., Raleigh, North Carolina, USA.
BACKGROUND & AIMS:
Rifaximin is a gut-selective, oral antimicrobial agent shown to reduce recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use.
We conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, n= 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n=140).
In the all-rifaximin population, median exposure was 427.0 days (range, 2-1427 days), with 510.5 person-y of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure, (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72).
Long-term treatment (≥24 months) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920.